Charles M. Rice

Bovine Viral Diarrhea Virus Core Is an Intrinsically Disordered Protein That Binds RNA � (2007)

Catherine L. Murray, Joseph Marcotrigiano, Charles M. Rice

Pestiviruses, including bovine viral diarrhea virus (BVDV), are important animal pathogens and close relatives of hepatitis C virus. Pestivirus particles are composed of an RNA genome, a host-derived...

euHCVdb: the European hepatitis C virus database (2007)

Combet, Christophe, Garnier, Nicolas, Charavay, Céline, Grando, Delphine, Crisan, Daniel, Lopez, Julien, ...

The hepatitis C virus (HCV) genome shows remarkable sequence variability, leading to the classification of at least six major genotypes, numerous subtypes and a myriad of quasispecies within a given...

Nucleic Acids Research Advance Access published November 16, 2006 euHCVdb: the European hepatitis C virus database (2006)

Christophe Combet, Nicolas Garnier, Céline Charavay, Delphine Gr, Daniel Crisan, Julien Lopez, ...

The hepatitis C virus (HCV) genome shows remarkable sequence variability, leading to the classification of at least six major genotypes, numerous subtypes and a myriad of quasispecies within a given...

euHCVdb: the European hepatitis C virus database (2006)

Combet, Christophe, Garnier, Nicolas, Charavay, Céline, Grando, Delphine, Crisan, Daniel, Lopez, Julien, ...

The hepatitis C virus (HCV) genome shows remarkable sequence variability, leading to the classification of at least six major genotypes, numerous subtypes and a myriad of quasispecies within a given...

euHCVdb: the European hepatitis C virus database (2006)

Combet, Christophe, Garnier, Nicolas, Charavay, Céline, Grando, Delphine, Crisan, Daniel, Lopez, Julien, ...

The hepatitis C virus (HCV) genome shows remarkable sequence variability, leading to the classification of at least six major genotypes, numerous subtypes and a myriad of quasispecies within a given...

Sindbis virus ts103 has a mutation in glycoprotein E2 that leads to defective assembly of virions (1989)

Hahn, Chang S., Rice, Charles M., Strauss, Ellen G., Lenches, Edith M., Strauss, James H.

Sindbis virus mutant ts103 is aberrant in the assembly of virus particles. During virus budding, proper nucleocapsid-glycoprotein interactions fail to occur such that particles containing many...

Mapping of RNA- temperature-sensitive mutants of Sindbis virus: complementation group F mutants have lesions in nsP4 (1989)

Hahn, Young S., Grakoui, Arash, Rice, Charles M., Strauss, Ellen G., Strauss, James H.

Temperature-sensitive (ts) mutants of Sindbis virus belonging to complementation group F, ts6, ts110, and ts118, are defective in RNA synthesis at the nonpermissive temperature. cDNA clones of these...

Production of infectious RNA transcripts from Sindbis virus cDNA clones: mapping of lethal mutations, rescue of a temperature-sensitive marker, and in vitro mutagenesis to generate defined mutants (1987)

Rice, Charles M., Levis, Robin, Strauss, James H., Huang, Henry V.

We constructed full-length cDNA clones of Sindbis virus that can be transcribed in vitro by SP6 RNA polymerase to produce infectious genome-length transcripts. Viruses produced from in vitro...

Comparison of the Virulent Asibi Strain of Yellow Fever Virus with the 17D Vaccine Strain Derived from It (1987)

Hahn, Chang S., Dalrymple, Joel M., Strauss, James H., Rice, Charles M.

We have sequenced the virulent Asibi strain of yellow fever virus and compared this sequence to that of the 17D vaccine strain, which was derived from it. These two strains of viruses differ by more...

Expression of Sindbis virus structural proteins via recombinant vaccinia virus: synthesis, processing, and incorporation into mature Sindbis virions (1985)

Rice, Charles M., Franke, Christine A., Strauss, James H., Hruby, Dennis E.

We have obtained a vaccinia virus recombinant which contains a complete cDNA copy of the 26S RNA of Sindbis virus within the thymidine kinase gene of the vaccinia virus genome. This recombinant...

Neomycin resistance as a dominant selectable marker for selection and isolation of vaccinia virus recombinants (1985)

Franke, Christine A., Rice, Charles M., Strauss, James H., Hruby, Dennis E.

The antibiotic G418 was shown to be an effective inhibitor of vaccinia virus replication when an appropriate concentration of it was added to cell monolayers 48 h before infection. Genetic...

Sindbis virus proteins nsP1 and nsP2 contain homology to nonstructural proteins from several RNA plant viruses (1985)

Ahlquist, Paul, Strauss, Ellen G., Rice, Charles M., Strauss, James H., Haseloff, James, Zimmern, David

Although the genetic organization of tobacco mosaic virus (TMV) differs considerably from that of the tripartite viruses (alfalfa mosaic virus [AlMV] and brome mosaic virus [BMV]), all of these RNA...

Sequence Studies of Several Alphavirus Genomic RNAs in the Region Containing the Start of the Subgenomic RNA (1982)

Ou, Jing-Hsiung, Rice, Charles M., Dalgarno, Lynn, Strauss, Ellen G., Strauss, James H.

The alphaviruses produce two mRNAs after infection: the genomic (49S) RNA which is translated into the nonstructural (replicase) proteins and the subgenomic (26S) RNA which serves as the mRNA for the...

Nucleotide Sequence of the 26S mRNA of Sindbis Virus and Deduced Sequence of the Encoded Virus Structural Proteins (1981)

Rice, Charles M., Strauss, James H.

The nucleotide sequence of intracellular 26S mRNA of Sindbis virus has been determined by direct sequence analysis of the cDNA made to this RNA with reverse transcriptase. From this, the amino acid...

Mechanism of action of a pestivirus antiviral compound

Baginski, Scott G., Pevear, Daniel C., Seipel, Marty, Sun, Siu Chi Chang, Benetatos, Christopher A., Chunduru, Srinivas K., ...

We report here the discovery of a small molecule inhibitor of pestivirus replication. The compound, designated VP32947, inhibits the replication of bovine viral diarrhea virus (BVDV) in cell culture...

Noncytopathic Sindbis virus RNA vectors for heterologous gene expression

Agapov, Eugene V., Frolov, Ilya, Lindenbach, Brett D., Prágai, Béla M., Schlesinger, Sondra, Rice, Charles M.

Infection of vertebrate cells with alphaviruses normally leads to prodigious expression of virus-encoded genes and a dramatic inhibition of host protein synthesis. Recombinant Sindbis viruses and...

Yellow Fever/Japanese Encephalitis Chimeric Viruses: Construction and Biological Properties

Chambers, Thomas J., Nestorowicz, Ann, Mason, Peter W., Rice, Charles M.

A system has been developed for generating chimeric yellow fever/Japanese encephalitis (YF/JE) viruses from cDNA templates encoding the structural proteins prM and E of JE virus within the backbone...

Long-Term Follow-Up of Chimpanzees Inoculated with the First Infectious Clone for Hepatitis C Virus

Major, Marian E., Mihalik, Kathleen, Fernandez, Javier, Seidman, Jessica, Kleiner, David, Kolykhalov, Alexander A., ...

Two chimpanzees (Ch1535 and Ch1536) became infected with hepatitis C virus (HCV) following intrahepatic inoculation with RNA transcribed from a full-length cDNA clone of the virus. Both animals were...

Selection of RNA Replicons Capable of Persistent Noncytopathic Replication in Mammalian Cells

Frolov, Ilya, Agapov, Eugene, Hoffman, Thomas A., Prágai, Béla M., Lippa, Mara, Schlesinger, Sondra, ...

The natural life cycle of alphaviruses, a group of plus-strand RNA viruses, involves transmission to vertebrate hosts via mosquitoes. Chronic infections are established in mosquitoes (and usually in...

Template-Dependent Initiation of Sindbis Virus RNA Replication In Vitro

Lemm, Julie A., Bergqvist, Anders, Read, Carol M., Rice, Charles M.

Recent insights into the early events in Sindbis virus RNA replication suggest a requirement for either the P123 or P23 polyprotein, as well as mature nsP4, the RNA-dependent RNA polymerase, for...

Infectious Bovine Viral Diarrhea Virus (Strain NADL) RNA from Stable cDNA Clones: a Cellular Insert Determines NS3 Production and Viral Cytopathogenicity

Mendez, Ernesto, Ruggli, Nicolas, Collett, Marc S., Rice, Charles M.

Bovine viral diarrhea virus (BVDV), strain NADL, was originally isolated from an animal with fatal mucosal disease. This isolate is cytopathic in cell culture and produces two forms of NS3-containing...

The NS5A/NS5 Proteins of Viruses from Three Genera of the Family Flaviviridae Are Phosphorylated by Associated Serine/Threonine Kinases

Reed, Karen E., Gorbalenya, Alexander E., Rice, Charles M.

Phosphorylation of the expressed NS5A protein of hepatitis C virus (HCV), a member of the Hepacivirus genus of the family Flaviviridae, has been demonstrated in mammalian cells and in a cell-free...

Mutagenesis of the Signal Sequence of Yellow Fever Virus prM Protein: Enhancement of Signalase Cleavage In Vitro Is Lethal for Virus Production

Lee, Eva, Stocks, Christine E., Amberg, Sean M., Rice, Charles M., Lobigs, Mario

Proteolytic processing at the C-prM junction in the flavivirus polyprotein involves coordinated cleavages at the cytoplasmic and luminal sides of an internal signal sequence. We have introduced at...

Hepatitis C Virus-Encoded Enzymatic Activities and Conserved RNA Elements in the 3′ Nontranslated Region Are Essential for Virus Replication In Vivo

Kolykhalov, Alexander A., Mihalik, Kathy, Feinstone, Stephen M., Rice, Charles M.

Hepatitis C virus (HCV) infection is a widespread major human health concern. Significant obstacles in the study of this virus include the absence of a reliable tissue culture system and a...

Subcellular Localization, Stability, and trans-Cleavage Competence of the Hepatitis C Virus NS3-NS4A Complex Expressed in Tetracycline-Regulated Cell Lines

Wölk, Benno, Sansonno, Domenico, Kräusslich, Hans-Georg, Dammacco, Franco, Rice, Charles M., Blum, Hubert E., ...

A tetracycline-regulated gene expression system and a panel of novel monoclonal antibodies were used to examine the subcellular localization, stability, and trans-cleavage competence of the hepatitis...

Genetic Interaction of Flavivirus Nonstructural Proteins NS1 and NS4A as a Determinant of Replicase Function

Lindenbach, Brett D., Rice, Charles M.

Nonstructural protein 1 (NS1) of yellow fever virus (YF) is a glycoprotein localized to extracytoplasmic compartments within infected cells. We have previously shown that NS1 can be supplied in trans...

Mutagenesis of the NS2B-NS3-Mediated Cleavage Site in the Flavivirus Capsid Protein Demonstrates a Requirement for Coordinated Processing

Amberg, Sean M., Rice, Charles M.

Analysis of flavivirus polyprotein processing has revealed the presence of a substrate for the virus-encoded NS2B-NS3 protease at the carboxy-terminal end of the C (capsid or core) protein. Cleavage...

A Single Nucleotide Change in the 5′ Noncoding Region of Sindbis Virus Confers Neurovirulence in Rats

Kobiler, David, Rice, Charles M., Brodie, Chaya, Shahar, Abraham, Dubuisson, Jean, Halevy, Menahem, ...

Two pairs of Sindbis virus (SV) variants that differ in their neuroinvasive and neurovirulent traits in mice have been isolated. Recently, we mapped the genetic determinants responsible for...

Transcriptional Activation of the Interleukin-2 Promoter by Hepatitis C Virus Core Protein

Bergqvist, Anders, Rice, Charles M.

Most patients infected with hepatitis C virus (HCV) become chronic carriers. Viruses that efficiently establish persistent infections must have effective ways of evading host defenses. In the case of...

Efficient Translation Initiation Is Required for Replication of Bovine Viral Diarrhea Virus Subgenomic Replicons

Myers, Tina M., Kolupaeva, Victoria G., Mendez, Ernesto, Baginski, Scott G., Frolov, Ilya, Hellen, Christopher U. T., ...

An internal ribosome entry site (IRES) mediates translation initiation of bovine viral diarrhea virus (BVDV) RNA. Studies have suggested that a portion of the Npro open reading frame (ORF) is...

Isolation and Characterization of Noncytopathic Pestivirus Mutants Reveals a Role for Nonstructural Protein NS4B in Viral Cytopathogenicity

Qu, Lin, McMullan, Laura K., Rice, Charles M.

Isolates of bovine viral diarrhea virus (BVDV), the prototype pestivirus, are divided into cytopathic (cp) and noncytopathic (ncp) biotypes according to their effect on cultured cells. The cp viruses...

Mutations in the Yellow Fever Virus Nonstructural Protein NS2A Selectively Block Production of Infectious Particles

Kümmerer, Beate M., Rice, Charles M.

Little is known about the function of flavivirus nonstructural protein NS2A. Two forms of NS2A are found in yellow fever virus-infected cells. Full-length NS2A (224 amino acids) is the product of...

Molecular and Immunological Significance of Chimpanzee Major Histocompatibility Complex Haplotypes for Hepatitis C Virus Immune Response and Vaccination Studies

Mizukoshi, Eishiro, Nascimbeni, Michelina, Blaustein, Joshua B., Mihalik, Kathleen, Rice, Charles M., Liang, T. Jake, ...

The chimpanzee is a critical animal model for studying cellular immune responses to infectious pathogens such as hepatitis B and C viruses, human immunodeficiency virus, and malaria. Several...

Previously Infected and Recovered Chimpanzees Exhibit Rapid Responses That Control Hepatitis C Virus Replication upon Rechallenge

Major, Marian E., Mihalik, Kathleen, Puig, Montserrat, Rehermann, Barbara, Nascimbeni, Michelina, Rice, Charles M., ...

Responses in three chimpanzees were compared following challenge with a clonal hepatitis C virus (HCV) contained in plasma from an animal that had received infectious RNA transcripts. Two of the...

Characterization of Vesicular Stomatitis Virus Recombinants That Express and Incorporate High Levels of Hepatitis C Virus Glycoproteins

Buonocore, Linda, Blight, Keril J., Rice, Charles M., Rose, John K.

We generated recombinant vesicular stomatitis viruses (VSV) expressing genes encoding hybrid proteins consisting of the extracellular domains of hepatitis C virus (HCV) glycoproteins fused at...

Highly Permissive Cell Lines for Subgenomic and Genomic Hepatitis C Virus RNA Replication

Blight, Keril J., McKeating, Jane A., Rice, Charles M.

Hepatitis C virus (HCV) replication appears to be restricted to the human hepatoma cell line Huh-7, indicating that a favorable cellular environment exists within these cells. Although adaptive...

Roles of Nonstructural Protein nsP2 and Alpha/Beta Interferons in Determining the Outcome of Sindbis Virus Infection

Frolova, Elena I., Fayzulin, Rafik Z., Cook, Susan H., Griffin, Diane E., Rice, Charles M., Frolov, Ilya

Alphaviruses productively infect a variety of vertebrate and insect cell lines. In vertebrate cells, Sindbis virus redirects cellular processes to meet the needs of virus propagation. At the same...

Hepatitis C Virus RNA Synthesis in a Cell-Free System Isolated from Replicon-Containing Hepatoma Cells

Hardy, Richard W., Marcotrigiano, Joseph, Blight, Keril J., Majors, John E., Rice, Charles M.

A number of hepatitis C virus (HCV) proteins, including NS5B, the RNA-dependent RNA polymerase, were detected in membrane fractions from Huh7 cells containing autonomously replicating HCV RNA...

Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs

Randall, Glenn, Grakoui, Arash, Rice, Charles M.

RNA interference is a cellular process of gene silencing in which small duplexes of RNA specifically target a homologous sequence for cleavage by cellular ribonucleases. The introduction of ≈22-nt...

Efficient Replication of Hepatitis C Virus Genotype 1a RNAs in Cell Culture

Blight, Keril J., McKeating, Jane A., Marcotrigiano, Joseph, Rice, Charles M.

Hepatitis C virus (HCV) genotype 1 (subtypes 1a and 1b) is responsible for the majority of treatment-resistant liver disease worldwide. Thus far, efficient HCV RNA replication has been observed only...

Hepatitis C Virus Glycoproteins Interact with DC-SIGN and DC-SIGNR

Pöhlmann, Stefan, Zhang, Jie, Baribaud, Frédéric, Chen, Zhiwei, Leslie, George J., Lin, George, ...

DC-SIGN and DC-SIGNR are two closely related membrane-associated C-type lectins that bind human immunodeficiency virus (HIV) envelope glycoprotein with high affinity. Binding of HIV to cells...

Kinetics of CD4+ and CD8+ Memory T-Cell Responses during Hepatitis C Virus Rechallenge of Previously Recovered Chimpanzees

Nascimbeni, Michelina, Mizukoshi, Eishiro, Bosmann, Markus, Major, Marian E., Mihalik, Kathleen, Rice, Charles M., ...

The immunological correlates of hepatitis C virus (HCV)-specific immunity are not well understood. Antibodies to HCV structural proteins do not appear to play a key role in clearance of the virus and...

Amphipathic Helix-Dependent Localization of NS5A Mediates Hepatitis C Virus RNA Replication

Elazar, Menashe, Cheong, Kwang Ho, Liu, Ping, Greenberg, Harry B., Rice, Charles M., Glenn, Jeffrey S.

We identified an N-terminal amphipathic helix (AH) in one of hepatitis C virus (HCV)’s nonstructural proteins, NS5A. This AH is necessary and sufficient for membrane localization and is conserved...

Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles

Hsu, Mayla, Zhang, Jie, Flint, Mike, Logvinoff, Carine, Cheng-Mayer, Cecilia, Rice, Charles M., ...

HIV pseudotypes bearing native hepatitis C virus (HCV) glycoproteins (strain H and Con1) are infectious for the human hepatoma cell lines Huh-7 and PLC/PR5. Infectivity depends on coexpression of...

Expression of the Zinc-Finger Antiviral Protein Inhibits Alphavirus Replication

Bick, Matthew J., Carroll, John-William N., Gao, Guangxia, Goff, Stephen P., Rice, Charles M., MacDonald, Margaret R.

The rat zinc-finger antiviral protein (ZAP) was recently identified as a host protein conferring resistance to retroviral infection. We analyzed ZAP's ability to inhibit viruses from other families...

Selection of Functional 5′ cis-Acting Elements Promoting Efficient Sindbis Virus Genome Replication

Gorchakov, Rodion, Hardy, Richard, Rice, Charles M., Frolov, Ilya

The 5′ portion of the Sindbis virus (SIN) genome RNA is multifunctional. Besides initiating translation of the nonstructural polyprotein, RNA elements in the 5′ 200 bases of the SIN genome RNA,...

A cis-Acting Replication Element in the Sequence Encoding the NS5B RNA-Dependent RNA Polymerase Is Required for Hepatitis C Virus RNA Replication

You, Shihyun, Stump, Decherd D., Branch, Andrea D., Rice, Charles M.

RNA structures play key roles in the replication of RNA viruses. Sequence alignment software, thermodynamic RNA folding programs, and classical comparative phylogenetic analysis were used to build...

CD81 Is Required for Hepatitis C Virus Glycoprotein-Mediated Viral Infection

Zhang, Jie, Randall, Glenn, Higginbottom, Adrian, Monk, Peter, Rice, Charles M., McKeating, Jane A.

CD81 has been described as a putative receptor for hepatitis C virus (HCV); however, its role in HCV cell entry has not been characterized due to the lack of an efficient cell culture system. We have...

Uncleaved NS2-3 Is Required for Production of Infectious Bovine Viral Diarrhea Virus

Agapov, Eugene V., Murray, Catherine L., Frolov, Ilya, Qu, Lin, Myers, Tina M., Rice, Charles M.

Despite increasing characterization of pestivirus-encoded proteins, functions for nonstructural (NS) proteins NS2, NS2-3, NS4B, and NS5A have not yet been reported. Here we investigated the function...

Characterization of Infectious Retroviral Pseudotype Particles Bearing Hepatitis C Virus Glycoproteins

Flint, Mike, Logvinoff, Carine, Rice, Charles M., McKeating, Jane A.

The recent development of infectious retroviral pseudotypes bearing hepatitis C virus (HCV) glycoproteins represents an opportunity to study the functionally active form of the HCV E1 and E2...

Insertion of Green Fluorescent Protein into Nonstructural Protein 5A Allows Direct Visualization of Functional Hepatitis C Virus Replication Complexes†

Moradpour, Darius, Evans, Matthew J., Gosert, Rainer, Yuan, Zhenghong, Blum, Hubert E., Goff, Stephen P., ...

Hepatitis C virus (HCV) replicates its genome in a membrane-associated replication complex, composed of viral proteins, replicating RNA and altered cellular membranes. We describe here HCV replicons...

Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity

Chang, Hao-Ming, Paulson, Matthew, Holko, Michelle, Rice, Charles M., Williams, Bryan R. G., Marié, Isabelle, ...

Histone deacetylase (HDAC) activity, commonly correlated with transcriptional repression, was essential for transcriptional induction of IFN-stimulated genes (ISG). Inhibition of HDAC function led to...

PKR-Dependent and -Independent Mechanisms Are Involved in Translational Shutoff during Sindbis Virus Infection

Gorchakov, Rodion, Frolova, Elena, Williams, Bryan R. G., Rice, Charles M., Frolov, Ilya

The replication of Sindbis virus (SIN) profoundly affects the metabolism of infected vertebrate cells. One of the main events during SIN infection is the strong inhibition of translation of cellular...

Long-Term Persistence of Infection in Chimpanzees Inoculated with an Infectious Hepatitis C Virus Clone Is Associated with a Decrease in the Viral Amino Acid Substitution Rate and Low Levels of Heterogeneity

Fernandez, Javier, Taylor, Deborah, Morhardt, Duncan R., Mihalik, Kathleen, Puig, Montserrat, Rice, Charles M., ...

Two chimpanzees, 1535 and 1536, became persistently infected following inoculation with RNA transcripts from cDNA clones of hepatitis C virus (HCV). Analysis of the HCV genomes from both animals...

Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication

Evans, Matthew J., Rice, Charles M., Goff, Stephen P.

The study of the hepatitis C virus (HCV) has been hindered by the lack of in vitro model systems. The recent development of HCV subgenomic RNA replicons has permitted the study of viral RNA...

An N-Terminal Amphipathic Helix in Hepatitis C Virus (HCV) NS4B Mediates Membrane Association, Correct Localization of Replication Complex Proteins, and HCV RNA Replication

Elazar, Menashe, Liu, Ping, Rice, Charles M., Glenn, Jeffrey S.

Like other positive-strand RNA viruses, hepatitis C virus (HCV) is believed to replicate its RNA in association with host cell cytoplasmic membranes. Because of its association with such membranes,...

Hepatitis C Virus Core Protein Associates with Detergent-Resistant Membranes Distinct from Classical Plasma Membrane Rafts

Matto, Meirav, Rice, Charles M., Aroeti, Benjamin, Glenn, Jeffrey S.

A subpopulation of hepatitis C virus (HCV) core protein in cells harboring full-length HCV replicons is biochemically associated with detergent-resistant membranes (DRMs) in a manner similar to that...

Genetic Interactions between Hepatitis C Virus Replicons

Evans, Matthew J., Rice, Charles M., Goff, Stephen P.

To investigate interactions between hepatitis C virus (HCV) RNA replication complexes, a system was developed to simultaneously select different HCV subgenomic replicons within the same cell....

Requirements at the 3′ End of the Sindbis Virus Genome for Efficient Synthesis of Minus-Strand RNA

Hardy, Richard W., Rice, Charles M.

The 3′-untranslated region of the Sindbis virus genome is 0.3 kb in length with a 19-nucleotide conserved sequence element (3′ CSE) immediately preceding the 3′-poly(A) tail. The 3′ CSE and...

Dual Mechanisms of Pestiviral Superinfection Exclusion at Entry and RNA Replication

Lee, Young-Min, Tscherne, Donna M., Yun, Sang-Im, Frolov, Ilya, Rice, Charles M.

For many viruses, primary infection has been shown to prevent superinfection by a homologous second virus. In this study, we investigated superinfection exclusion of bovine viral diarrhea virus...

Liver-Directed Gamma Interferon Gene Delivery in Chronic Hepatitis C

Shin, Eui-Cheol, Protzer, Ulrike, Untergasser, Andreas, Feinstone, Stephen M., Rice, Charles M., Hasselschwert, Dana, ...

Gamma interferon (IFN-γ) has been shown to inhibit replication of subgenomic and genomic hepatitis C virus (HCV) RNAs in vitro and to noncytolytically suppress hepatitis B virus (HBV) replication in...

Development and Application of a Reverse Genetics System for Japanese Encephalitis Virus

Yun, Sang-Im, Kim, Seok-Yong, Rice, Charles M., Lee, Young-Min

Japanese encephalitis virus (JEV) is a common agent of viral encephalitis that causes high mortality and morbidity among children. Molecular genetic studies of JEV are hampered by the lack of a...

Structure of the Zinc-Binding Domain of an Essential Replicase Component of Hepatitis C Virus Reveals a Novel Fold

Tellinghuisen, Timothy L., Marcotrigiano, Joseph, Rice, Charles M.

Hepatitis C virus (HCV) is a human pathogen affecting nearly 3% of the world’s population1. Chronic infections can lead to cirrhosis and liver cancer. The RNA replication machine of HCV is a...

Time- and Temperature-Dependent Activation of Hepatitis C Virus for Low-pH-Triggered Entry

Tscherne, Donna M., Jones, Christopher T., Evans, Matthew J., Lindenbach, Brett D., McKeating, Jane A., Rice, Charles M.

Hepatitis C virus (HCV) is an important human pathogen associated with chronic liver disease. Recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and...

Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro

Lindenbach, Brett D., Meuleman, Philip, Ploss, Alexander, Vanwolleghem, Thomas, Syder, Andrew J., McKeating, Jane A., ...

Hepatitis C virus (HCV) is a major cause of chronic liver disease, frequently progressing to cirrhosis and increased risk of hepatocellular carcinoma. Current therapies are inadequate and progress in...

Virus-induced type I IFN stimulates generation of immunoproteasomes at the site of infection

Shin, Eui-Cheol, Seifert, Ulrike, Kato, Takanobu, Rice, Charles M., Feinstone, Stephen M., Kloetzel, Peter-M., ...

IFN-γ is known as the initial and primary inducer of immunoproteasomes during viral infections. We now report that type I IFN induced the transcription and translation of immunoproteasome subunits,...

The NS5A Protein of Bovine Viral Diarrhea Virus Contains an Essential Zinc-Binding Site Similar to That of the Hepatitis C Virus NS5A Protein

Tellinghuisen, Timothy L., Paulson, Matthew S., Rice, Charles M.

The recent demonstration that the NS5A protein of hepatitis C virus (HCV) contains an unconventional zinc-binding site with the format Cx17CxCx20C and the presence of a similar sequence element in...

Mechanism of action of a pestivirus antiviral compound

Baginski, Scott G., Pevear, Daniel C., Seipel, Marty, Sun, Siu Chi Chang, Benetatos, Christopher A., Chunduru, Srinivas K., ...

We report here the discovery of a small molecule inhibitor of pestivirus replication. The compound, designated VP32947, inhibits the replication of bovine viral diarrhea virus (BVDV) in cell culture...

Noncytopathic Sindbis virus RNA vectors for heterologous gene expression

Agapov, Eugene V., Frolov, Ilya, Lindenbach, Brett D., Prágai, Béla M., Schlesinger, Sondra, Rice, Charles M.

Infection of vertebrate cells with alphaviruses normally leads to prodigious expression of virus-encoded genes and a dramatic inhibition of host protein synthesis. Recombinant Sindbis viruses and...

Yellow Fever/Japanese Encephalitis Chimeric Viruses: Construction and Biological Properties

Chambers, Thomas J., Nestorowicz, Ann, Mason, Peter W., Rice, Charles M.

A system has been developed for generating chimeric yellow fever/Japanese encephalitis (YF/JE) viruses from cDNA templates encoding the structural proteins prM and E of JE virus within the backbone...

Long-Term Follow-Up of Chimpanzees Inoculated with the First Infectious Clone for Hepatitis C Virus

Major, Marian E., Mihalik, Kathleen, Fernandez, Javier, Seidman, Jessica, Kleiner, David, Kolykhalov, Alexander A., ...

Two chimpanzees (Ch1535 and Ch1536) became infected with hepatitis C virus (HCV) following intrahepatic inoculation with RNA transcribed from a full-length cDNA clone of the virus. Both animals were...

Selection of RNA Replicons Capable of Persistent Noncytopathic Replication in Mammalian Cells

Frolov, Ilya, Agapov, Eugene, Hoffman, Thomas A., Prágai, Béla M., Lippa, Mara, Schlesinger, Sondra, ...

The natural life cycle of alphaviruses, a group of plus-strand RNA viruses, involves transmission to vertebrate hosts via mosquitoes. Chronic infections are established in mosquitoes (and usually in...

Template-Dependent Initiation of Sindbis Virus RNA Replication In Vitro

Lemm, Julie A., Bergqvist, Anders, Read, Carol M., Rice, Charles M.

Recent insights into the early events in Sindbis virus RNA replication suggest a requirement for either the P123 or P23 polyprotein, as well as mature nsP4, the RNA-dependent RNA polymerase, for...

Infectious Bovine Viral Diarrhea Virus (Strain NADL) RNA from Stable cDNA Clones: a Cellular Insert Determines NS3 Production and Viral Cytopathogenicity

Mendez, Ernesto, Ruggli, Nicolas, Collett, Marc S., Rice, Charles M.

Bovine viral diarrhea virus (BVDV), strain NADL, was originally isolated from an animal with fatal mucosal disease. This isolate is cytopathic in cell culture and produces two forms of NS3-containing...

The NS5A/NS5 Proteins of Viruses from Three Genera of the Family Flaviviridae Are Phosphorylated by Associated Serine/Threonine Kinases

Reed, Karen E., Gorbalenya, Alexander E., Rice, Charles M.

Phosphorylation of the expressed NS5A protein of hepatitis C virus (HCV), a member of the Hepacivirus genus of the family Flaviviridae, has been demonstrated in mammalian cells and in a cell-free...

Mutagenesis of the Signal Sequence of Yellow Fever Virus prM Protein: Enhancement of Signalase Cleavage In Vitro Is Lethal for Virus Production

Lee, Eva, Stocks, Christine E., Amberg, Sean M., Rice, Charles M., Lobigs, Mario

Proteolytic processing at the C-prM junction in the flavivirus polyprotein involves coordinated cleavages at the cytoplasmic and luminal sides of an internal signal sequence. We have introduced at...

Hepatitis C Virus-Encoded Enzymatic Activities and Conserved RNA Elements in the 3′ Nontranslated Region Are Essential for Virus Replication In Vivo

Kolykhalov, Alexander A., Mihalik, Kathy, Feinstone, Stephen M., Rice, Charles M.

Hepatitis C virus (HCV) infection is a widespread major human health concern. Significant obstacles in the study of this virus include the absence of a reliable tissue culture system and a...

Subcellular Localization, Stability, and trans-Cleavage Competence of the Hepatitis C Virus NS3-NS4A Complex Expressed in Tetracycline-Regulated Cell Lines

Wölk, Benno, Sansonno, Domenico, Kräusslich, Hans-Georg, Dammacco, Franco, Rice, Charles M., Blum, Hubert E., ...

A tetracycline-regulated gene expression system and a panel of novel monoclonal antibodies were used to examine the subcellular localization, stability, and trans-cleavage competence of the hepatitis...

Genetic Interaction of Flavivirus Nonstructural Proteins NS1 and NS4A as a Determinant of Replicase Function

Lindenbach, Brett D., Rice, Charles M.

Nonstructural protein 1 (NS1) of yellow fever virus (YF) is a glycoprotein localized to extracytoplasmic compartments within infected cells. We have previously shown that NS1 can be supplied in trans...

Mutagenesis of the NS2B-NS3-Mediated Cleavage Site in the Flavivirus Capsid Protein Demonstrates a Requirement for Coordinated Processing

Amberg, Sean M., Rice, Charles M.

Analysis of flavivirus polyprotein processing has revealed the presence of a substrate for the virus-encoded NS2B-NS3 protease at the carboxy-terminal end of the C (capsid or core) protein. Cleavage...

A Single Nucleotide Change in the 5′ Noncoding Region of Sindbis Virus Confers Neurovirulence in Rats

Kobiler, David, Rice, Charles M., Brodie, Chaya, Shahar, Abraham, Dubuisson, Jean, Halevy, Menahem, ...

Two pairs of Sindbis virus (SV) variants that differ in their neuroinvasive and neurovirulent traits in mice have been isolated. Recently, we mapped the genetic determinants responsible for...

Transcriptional Activation of the Interleukin-2 Promoter by Hepatitis C Virus Core Protein

Bergqvist, Anders, Rice, Charles M.

Most patients infected with hepatitis C virus (HCV) become chronic carriers. Viruses that efficiently establish persistent infections must have effective ways of evading host defenses. In the case of...

Efficient Translation Initiation Is Required for Replication of Bovine Viral Diarrhea Virus Subgenomic Replicons

Myers, Tina M., Kolupaeva, Victoria G., Mendez, Ernesto, Baginski, Scott G., Frolov, Ilya, Hellen, Christopher U. T., ...

An internal ribosome entry site (IRES) mediates translation initiation of bovine viral diarrhea virus (BVDV) RNA. Studies have suggested that a portion of the Npro open reading frame (ORF) is...

Isolation and Characterization of Noncytopathic Pestivirus Mutants Reveals a Role for Nonstructural Protein NS4B in Viral Cytopathogenicity

Qu, Lin, McMullan, Laura K., Rice, Charles M.

Isolates of bovine viral diarrhea virus (BVDV), the prototype pestivirus, are divided into cytopathic (cp) and noncytopathic (ncp) biotypes according to their effect on cultured cells. The cp viruses...

Mutations in the Yellow Fever Virus Nonstructural Protein NS2A Selectively Block Production of Infectious Particles

Kümmerer, Beate M., Rice, Charles M.

Little is known about the function of flavivirus nonstructural protein NS2A. Two forms of NS2A are found in yellow fever virus-infected cells. Full-length NS2A (224 amino acids) is the product of...

Molecular and Immunological Significance of Chimpanzee Major Histocompatibility Complex Haplotypes for Hepatitis C Virus Immune Response and Vaccination Studies

Mizukoshi, Eishiro, Nascimbeni, Michelina, Blaustein, Joshua B., Mihalik, Kathleen, Rice, Charles M., Liang, T. Jake, ...

The chimpanzee is a critical animal model for studying cellular immune responses to infectious pathogens such as hepatitis B and C viruses, human immunodeficiency virus, and malaria. Several...

Previously Infected and Recovered Chimpanzees Exhibit Rapid Responses That Control Hepatitis C Virus Replication upon Rechallenge

Major, Marian E., Mihalik, Kathleen, Puig, Montserrat, Rehermann, Barbara, Nascimbeni, Michelina, Rice, Charles M., ...

Responses in three chimpanzees were compared following challenge with a clonal hepatitis C virus (HCV) contained in plasma from an animal that had received infectious RNA transcripts. Two of the...

Characterization of Vesicular Stomatitis Virus Recombinants That Express and Incorporate High Levels of Hepatitis C Virus Glycoproteins

Buonocore, Linda, Blight, Keril J., Rice, Charles M., Rose, John K.

We generated recombinant vesicular stomatitis viruses (VSV) expressing genes encoding hybrid proteins consisting of the extracellular domains of hepatitis C virus (HCV) glycoproteins fused at...

Highly Permissive Cell Lines for Subgenomic and Genomic Hepatitis C Virus RNA Replication

Blight, Keril J., McKeating, Jane A., Rice, Charles M.

Hepatitis C virus (HCV) replication appears to be restricted to the human hepatoma cell line Huh-7, indicating that a favorable cellular environment exists within these cells. Although adaptive...

Roles of Nonstructural Protein nsP2 and Alpha/Beta Interferons in Determining the Outcome of Sindbis Virus Infection

Frolova, Elena I., Fayzulin, Rafik Z., Cook, Susan H., Griffin, Diane E., Rice, Charles M., Frolov, Ilya

Alphaviruses productively infect a variety of vertebrate and insect cell lines. In vertebrate cells, Sindbis virus redirects cellular processes to meet the needs of virus propagation. At the same...

Hepatitis C Virus RNA Synthesis in a Cell-Free System Isolated from Replicon-Containing Hepatoma Cells

Hardy, Richard W., Marcotrigiano, Joseph, Blight, Keril J., Majors, John E., Rice, Charles M.

A number of hepatitis C virus (HCV) proteins, including NS5B, the RNA-dependent RNA polymerase, were detected in membrane fractions from Huh7 cells containing autonomously replicating HCV RNA...

Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs

Randall, Glenn, Grakoui, Arash, Rice, Charles M.

RNA interference is a cellular process of gene silencing in which small duplexes of RNA specifically target a homologous sequence for cleavage by cellular ribonucleases. The introduction of ≈22-nt...

Efficient Replication of Hepatitis C Virus Genotype 1a RNAs in Cell Culture

Blight, Keril J., McKeating, Jane A., Marcotrigiano, Joseph, Rice, Charles M.

Hepatitis C virus (HCV) genotype 1 (subtypes 1a and 1b) is responsible for the majority of treatment-resistant liver disease worldwide. Thus far, efficient HCV RNA replication has been observed only...

Hepatitis C Virus Glycoproteins Interact with DC-SIGN and DC-SIGNR

Pöhlmann, Stefan, Zhang, Jie, Baribaud, Frédéric, Chen, Zhiwei, Leslie, George J., Lin, George, ...

DC-SIGN and DC-SIGNR are two closely related membrane-associated C-type lectins that bind human immunodeficiency virus (HIV) envelope glycoprotein with high affinity. Binding of HIV to cells...

Kinetics of CD4+ and CD8+ Memory T-Cell Responses during Hepatitis C Virus Rechallenge of Previously Recovered Chimpanzees

Nascimbeni, Michelina, Mizukoshi, Eishiro, Bosmann, Markus, Major, Marian E., Mihalik, Kathleen, Rice, Charles M., ...

The immunological correlates of hepatitis C virus (HCV)-specific immunity are not well understood. Antibodies to HCV structural proteins do not appear to play a key role in clearance of the virus and...

Amphipathic Helix-Dependent Localization of NS5A Mediates Hepatitis C Virus RNA Replication

Elazar, Menashe, Cheong, Kwang Ho, Liu, Ping, Greenberg, Harry B., Rice, Charles M., Glenn, Jeffrey S.

We identified an N-terminal amphipathic helix (AH) in one of hepatitis C virus (HCV)’s nonstructural proteins, NS5A. This AH is necessary and sufficient for membrane localization and is conserved...

Development and Application of a Reverse Genetics System for Japanese Encephalitis Virus

Yun, Sang-Im, Kim, Seok-Yong, Rice, Charles M., Lee, Young-Min

Japanese encephalitis virus (JEV) is a common agent of viral encephalitis that causes high mortality and morbidity among children. Molecular genetic studies of JEV are hampered by the lack of a...

Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles

Hsu, Mayla, Zhang, Jie, Flint, Mike, Logvinoff, Carine, Cheng-Mayer, Cecilia, Rice, Charles M., ...

HIV pseudotypes bearing native hepatitis C virus (HCV) glycoproteins (strain H and Con1) are infectious for the human hepatoma cell lines Huh-7 and PLC/PR5. Infectivity depends on coexpression of...

Expression of the Zinc-Finger Antiviral Protein Inhibits Alphavirus Replication

Bick, Matthew J., Carroll, John-William N., Gao, Guangxia, Goff, Stephen P., Rice, Charles M., MacDonald, Margaret R.

The rat zinc-finger antiviral protein (ZAP) was recently identified as a host protein conferring resistance to retroviral infection. We analyzed ZAP's ability to inhibit viruses from other families...

Selection of Functional 5′ cis-Acting Elements Promoting Efficient Sindbis Virus Genome Replication

Gorchakov, Rodion, Hardy, Richard, Rice, Charles M., Frolov, Ilya

The 5′ portion of the Sindbis virus (SIN) genome RNA is multifunctional. Besides initiating translation of the nonstructural polyprotein, RNA elements in the 5′ 200 bases of the SIN genome RNA,...

A cis-Acting Replication Element in the Sequence Encoding the NS5B RNA-Dependent RNA Polymerase Is Required for Hepatitis C Virus RNA Replication

You, Shihyun, Stump, Decherd D., Branch, Andrea D., Rice, Charles M.

RNA structures play key roles in the replication of RNA viruses. Sequence alignment software, thermodynamic RNA folding programs, and classical comparative phylogenetic analysis were used to build...

CD81 Is Required for Hepatitis C Virus Glycoprotein-Mediated Viral Infection

Zhang, Jie, Randall, Glenn, Higginbottom, Adrian, Monk, Peter, Rice, Charles M., McKeating, Jane A.

CD81 has been described as a putative receptor for hepatitis C virus (HCV); however, its role in HCV cell entry has not been characterized due to the lack of an efficient cell culture system. We have...

Uncleaved NS2-3 Is Required for Production of Infectious Bovine Viral Diarrhea Virus

Agapov, Eugene V., Murray, Catherine L., Frolov, Ilya, Qu, Lin, Myers, Tina M., Rice, Charles M.

Despite increasing characterization of pestivirus-encoded proteins, functions for nonstructural (NS) proteins NS2, NS2-3, NS4B, and NS5A have not yet been reported. Here we investigated the function...

Characterization of Infectious Retroviral Pseudotype Particles Bearing Hepatitis C Virus Glycoproteins

Flint, Mike, Logvinoff, Carine, Rice, Charles M., McKeating, Jane A.

The recent development of infectious retroviral pseudotypes bearing hepatitis C virus (HCV) glycoproteins represents an opportunity to study the functionally active form of the HCV E1 and E2...

Insertion of Green Fluorescent Protein into Nonstructural Protein 5A Allows Direct Visualization of Functional Hepatitis C Virus Replication Complexes†

Moradpour, Darius, Evans, Matthew J., Gosert, Rainer, Yuan, Zhenghong, Blum, Hubert E., Goff, Stephen P., ...

Hepatitis C virus (HCV) replicates its genome in a membrane-associated replication complex, composed of viral proteins, replicating RNA and altered cellular membranes. We describe here HCV replicons...

Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity

Chang, Hao-Ming, Paulson, Matthew, Holko, Michelle, Rice, Charles M., Williams, Bryan R. G., Marié, Isabelle, ...

Histone deacetylase (HDAC) activity, commonly correlated with transcriptional repression, was essential for transcriptional induction of IFN-stimulated genes (ISG). Inhibition of HDAC function led to...

PKR-Dependent and -Independent Mechanisms Are Involved in Translational Shutoff during Sindbis Virus Infection

Gorchakov, Rodion, Frolova, Elena, Williams, Bryan R. G., Rice, Charles M., Frolov, Ilya

The replication of Sindbis virus (SIN) profoundly affects the metabolism of infected vertebrate cells. One of the main events during SIN infection is the strong inhibition of translation of cellular...

Long-Term Persistence of Infection in Chimpanzees Inoculated with an Infectious Hepatitis C Virus Clone Is Associated with a Decrease in the Viral Amino Acid Substitution Rate and Low Levels of Heterogeneity

Fernandez, Javier, Taylor, Deborah, Morhardt, Duncan R., Mihalik, Kathleen, Puig, Montserrat, Rice, Charles M., ...

Two chimpanzees, 1535 and 1536, became persistently infected following inoculation with RNA transcripts from cDNA clones of hepatitis C virus (HCV). Analysis of the HCV genomes from both animals...

Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication

Evans, Matthew J., Rice, Charles M., Goff, Stephen P.

The study of the hepatitis C virus (HCV) has been hindered by the lack of in vitro model systems. The recent development of HCV subgenomic RNA replicons has permitted the study of viral RNA...

An N-Terminal Amphipathic Helix in Hepatitis C Virus (HCV) NS4B Mediates Membrane Association, Correct Localization of Replication Complex Proteins, and HCV RNA Replication

Elazar, Menashe, Liu, Ping, Rice, Charles M., Glenn, Jeffrey S.

Like other positive-strand RNA viruses, hepatitis C virus (HCV) is believed to replicate its RNA in association with host cell cytoplasmic membranes. Because of its association with such membranes,...

Hepatitis C Virus Core Protein Associates with Detergent-Resistant Membranes Distinct from Classical Plasma Membrane Rafts

Matto, Meirav, Rice, Charles M., Aroeti, Benjamin, Glenn, Jeffrey S.

A subpopulation of hepatitis C virus (HCV) core protein in cells harboring full-length HCV replicons is biochemically associated with detergent-resistant membranes (DRMs) in a manner similar to that...

Genetic Interactions between Hepatitis C Virus Replicons

Evans, Matthew J., Rice, Charles M., Goff, Stephen P.

To investigate interactions between hepatitis C virus (HCV) RNA replication complexes, a system was developed to simultaneously select different HCV subgenomic replicons within the same cell....

Requirements at the 3′ End of the Sindbis Virus Genome for Efficient Synthesis of Minus-Strand RNA

Hardy, Richard W., Rice, Charles M.

The 3′-untranslated region of the Sindbis virus genome is 0.3 kb in length with a 19-nucleotide conserved sequence element (3′ CSE) immediately preceding the 3′-poly(A) tail. The 3′ CSE and...

Dual Mechanisms of Pestiviral Superinfection Exclusion at Entry and RNA Replication

Lee, Young-Min, Tscherne, Donna M., Yun, Sang-Im, Frolov, Ilya, Rice, Charles M.

For many viruses, primary infection has been shown to prevent superinfection by a homologous second virus. In this study, we investigated superinfection exclusion of bovine viral diarrhea virus...

Liver-Directed Gamma Interferon Gene Delivery in Chronic Hepatitis C

Shin, Eui-Cheol, Protzer, Ulrike, Untergasser, Andreas, Feinstone, Stephen M., Rice, Charles M., Hasselschwert, Dana, ...

Gamma interferon (IFN-γ) has been shown to inhibit replication of subgenomic and genomic hepatitis C virus (HCV) RNAs in vitro and to noncytolytically suppress hepatitis B virus (HBV) replication in...

Time- and Temperature-Dependent Activation of Hepatitis C Virus for Low-pH-Triggered Entry

Tscherne, Donna M., Jones, Christopher T., Evans, Matthew J., Lindenbach, Brett D., McKeating, Jane A., Rice, Charles M.

Hepatitis C virus (HCV) is an important human pathogen associated with chronic liver disease. Recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and...

Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro

Lindenbach, Brett D., Meuleman, Philip, Ploss, Alexander, Vanwolleghem, Thomas, Syder, Andrew J., McKeating, Jane A., ...

Hepatitis C virus (HCV) is a major cause of chronic liver disease, frequently progressing to cirrhosis and increased risk of hepatocellular carcinoma. Current therapies are inadequate and progress in...

The NS5A Protein of Bovine Viral Diarrhea Virus Contains an Essential Zinc-Binding Site Similar to That of the Hepatitis C Virus NS5A Protein

Tellinghuisen, Timothy L., Paulson, Matthew S., Rice, Charles M.

The recent demonstration that the NS5A protein of hepatitis C virus (HCV) contains an unconventional zinc-binding site with the format Cx17CxCx20C and the presence of a similar sequence element in...

Virus-induced type I IFN stimulates generation of immunoproteasomes at the site of infection

Shin, Eui-Cheol, Seifert, Ulrike, Kato, Takanobu, Rice, Charles M., Feinstone, Stephen M., Kloetzel, Peter-M., ...

IFN-γ is known as the initial and primary inducer of immunoproteasomes during viral infections. We now report that type I IFN induced the transcription and translation of immunoproteasome subunits,...

euHCVdb: the European hepatitis C virus database

Combet, Christophe, Garnier, Nicolas, Charavay, Céline, Grando, Delphine, Crisan, Daniel, Lopez, Julien, ...

The hepatitis C virus (HCV) genome shows remarkable sequence variability, leading to the classification of at least six major genotypes, numerous subtypes and a myriad of quasispecies within a given...

Diverse CD81 Proteins Support Hepatitis C Virus Infection▿

Flint, Mike, Von Hahn, Thomas, Zhang, Jie, Farquhar, Michelle, Jones, Christopher T., Balfe, Peter, ...

Hepatitis C virus (HCV) entry is dependent on CD81. To investigate whether the CD81 sequence is a determinant of HCV host range, we expressed a panel of diverse CD81 proteins and tested their ability...

Mathematical Modeling of Subgenomic Hepatitis C Virus Replication in Huh-7 Cells▿

Dahari, Harel, Ribeiro, Ruy M., Rice, Charles M., Perelson, Alan S.

Cell-based hepatitis C virus (HCV) replicon systems have provided a means for understanding HCV replication mechanisms and for testing new antiviral agents. We describe here a mathematical model of...

Plasma chemokine levels correlate with the outcome of antiviral therapy in patients with hepatitis C

Butera, David, Marukian, Svetlana, Iwamaye, Amy E., Hembrador, Edgardo, Chambers, Thomas J., Di Bisceglie, Adrian M., ...

Chronic infection with the hepatitis C virus (HCV) is associated with failures of T-cell–mediated immune clearance and with abnormal B-cell growth and activation. We examined the levels of...

Foxp3+CD4+CD25+ T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C

Manigold, Tobias, Shin, Eui-Cheol, Mizukoshi, Eishiro, Mihalik, Kathleen, Murthy, Krishna K., Rice, Charles M., ...

Hepatitis C virus (HCV) poses a global health problem because it readily establishes persistent infection and a vaccine is not available. CD4+CD25+ T cells have been implicated in HCV persistence...

Superinfection Exclusion in Cells Infected with Hepatitis C Virus▿

Tscherne, Donna M., Evans, Matthew J., Von Hahn, Thomas, Jones, Christopher T., Stamataki, Zania, McKeating, Jane A., ...

Superinfection exclusion is the ability of an established virus infection to interfere with infection by a second virus. In this study, we found that Huh-7.5 cells acutely infected with hepatitis C...

Evidence for a functional RNA element in the hepatitis C virus core gene

McMullan, Laura K., Grakoui, Arash, Evans, Matthew J., Mihalik, Kathleen, Puig, Montserrat, Branch, Andrea D., ...

In the core protein-coding region of hepatitis C virus (HCV), evidence exists for both phylogenetically conserved RNA structures and a +1 alternative reading frame (ARF). To investigate its role in...

High-Avidity Monoclonal Antibodies against the Human Scavenger Class B Type I Receptor Efficiently Block Hepatitis C Virus Infection in the Presence of High-Density Lipoprotein▿

Catanese, Maria Teresa, Graziani, Rita, Von Hahn, Thomas, Moreau, Martine, Huby, Thierry, Paonessa, Giacomo, ...

The human scavenger class B type 1 receptor (SR-B1/Cla1) was identified as a putative receptor for hepatitis C virus (HCV) because it binds to soluble recombinant HCV envelope glycoprotein E2 (sE2)....

Hepatitis C Virus p7 and NS2 Proteins Are Essential for Production of Infectious Virus▿

Jones, Christopher T., Murray, Catherine L., Eastman, Dawnnica K., Tassello, Jodie, Rice, Charles M.

Hepatitis C virus (HCV) infection is a global health concern affecting an estimated 3% of the world's population. Recently, cell culture systems have been established, allowing recapitulation of the...

Cellular cofactors affecting hepatitis C virus infection and replication

Randall, Glenn, Panis, Maryline, Cooper, Jacob D., Tellinghuisen, Timothy L., Sukhodolets, Karen E., Pfeffer, Sebastien, ...

Recently identified hepatitis C virus (HCV) isolates that are infectious in cell culture provide a genetic system to evaluate the significance of virus–host interactions for HCV replication. We...

The C Terminus of Hepatitis C Virus NS4A Encodes an Electrostatic Switch That Regulates NS5A Hyperphosphorylation and Viral Replication▿

Lindenbach, Brett D., Prágai, Béla M., Montserret, Roland, Beran, Rudolf K. F., Pyle, Anna M., Penin, François, ...

Hepatitis C virus (HCV) nonstructural protein 4A (NS4A) is only 54 amino acids (aa) in length, yet it is a key regulator of the essential serine protease and RNA helicase activities of the NS3-4A...

Alanine Scanning of the Hepatitis C Virus Core Protein Reveals Numerous Residues Essential for Production of Infectious Virus▿

Murray, Catherine L., Jones, Christopher T., Tassello, Jodie, Rice, Charles M.

Hepatitis C virus (HCV) is an important human pathogen affecting an estimated 3% of the world's population. Recent advances have enabled in vitro propagation of the virus and allow assembly and...

Yellow fever 17D as a vaccine vector for microbial CTL epitopes: protection in a rodent malaria model

Tao, Deng, Barba-Spaeth, Giovanna, Rai, Urvashi, Nussenzweig, Victor, Rice, Charles M., Nussenzweig, Ruth S.

The yellow fever vaccine 17D (17D) is safe, and after a single immunizing dose, elicits long-lasting, perhaps lifelong protective immunity. One of the major challenges facing delivery of human...

Live attenuated yellow fever 17D infects human DCs and allows for presentation of endogenous and recombinant T cell epitopes

Barba-Spaeth, Giovanna, Longman, Randy S., Albert, Matthew L., Rice, Charles M.

The yellow fever (YF) 17D vaccine is one of the most successful live attenuated vaccines available. A single immunization induces both long-lasting neutralizing antibody and YF-specific T cell...

Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients

Decalf, Jérémie, Fernandes, Sandrine, Longman, Randy, Ahloulay, Mina, Audat, Françoise, Lefrerre, François, ...

Plasmacytoid dendritic cells (pDCs) are the professional type I interferon (IFN)-producing cells, and upon activation they traffic to lymph organs, where they bridge innate and adaptive immunity....

3′ RNA Elements in Hepatitis C Virus Replication: Kissing Partners and Long Poly(U)▿

You, Shihyun, Rice, Charles M.

The hepatitis C virus (HCV) genomic RNA possesses conserved structural elements that are essential for its replication. The 3′ nontranslated region (NTR) contains several of these elements: a...

Bovine Viral Diarrhea Virus Core Is an Intrinsically Disordered Protein That Binds RNA▿

Murray, Catherine L., Marcotrigiano, Joseph, Rice, Charles M.

Pestiviruses, including bovine viral diarrhea virus (BVDV), are important animal pathogens and close relatives of hepatitis C virus. Pestivirus particles are composed of an RNA genome, a host-derived...

Identification of Residues Required for RNA Replication in Domains II and III of the Hepatitis C Virus NS5A Protein▿

Tellinghuisen, Timothy L., Foss, Katie L., Treadaway, Jason C., Rice, Charles M.

The NS5A protein of hepatitis C virus (HCV) plays an important but undefined role in viral RNA replication. NS5A has been proposed to be a three-domain protein, and the crystal structure of the...

Transdominant Inhibition of Bovine Viral Diarrhea Virus Entry▿

Tscherne, Donna M., Evans, Matthew J., MacDonald, Margaret R., Rice, Charles M.

Bovine viral diarrhea virus (BVDV) is a positive-strand RNA virus and a member of the genus Pestivirus in the family Flaviviridae. To identify and characterize essential factors required for BVDV...

Stable Cytotoxic T Cell Escape Mutation in Hepatitis C Virus Is Linked to Maintenance of Viral Fitness

Uebelhoer, Luke, Han, Jin-Hwan, Callendret, Benoit, Mateu, Guaniri, Shoukry, Naglaa H., Hanson, Holly L., ...

Mechanisms by which hepatitis C virus (HCV) evades cellular immunity to establish persistence in chronically infected individuals are not clear. Mutations in human leukocyte antigen (HLA) class...

Genomic Analysis Reveals a Potential Role for Cell Cycle Perturbation in HCV-Mediated Apoptosis of Cultured Hepatocytes

Walters, Kathie-Anne, Syder, Andrew J., Lederer, Sharon L., Diamond, Deborah L., Paeper, Bryan, Rice, Charles M., ...

The mechanisms of liver injury associated with chronic HCV infection, as well as the individual roles of both viral and host factors, are not clearly defined. However, it is becoming increasingly...

Clonal expansion of immunoglobulin M+CD27+ B cells in HCV-associated mixed cryoglobulinemia

Charles, Edgar D., Green, Rashidah M., Marukian, Svetlana, Talal, Andrew H., Lake-Bakaar, Gerond V., Jacobson, Ira M., ...

Hepatitis C virus (HCV) is associated with B-cell lymphoproliferative disorders such as mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). The pathogenesis of these disorders...

A Dynamic View of Hepatitis C Virus Replication Complexes▿ ‡

Wölk, Benno, Büchele, Benjamin, Moradpour, Darius, Rice, Charles M.

Hepatitis C virus (HCV) replicates its genome in a membrane-associated replication complex (RC). Specific membrane alterations, designated membranous webs, represent predominant sites of HCV RNA...

Internal Initiation Stimulates Production of p8 Minicore, a Member of a Newly Discovered Family of Hepatitis C Virus Core Protein Isoforms▿

Eng, Francis J., Walewski, Jose L., Klepper, Arielle L., Fishman, Sarah L., Desai, Suresh M., McMullan, Laura K., ...

The hepatitis C virus (HCV) core gene is more conserved at the nucleic acid level than is necessary to preserve the sequence of the core protein, suggesting that it contains information for...