Scientific Commons: E. Domingo

Major Atmospheric Gamma Imaging Cherenkov telescope is starting its operations with a set of engineering runs to tune the telescope subsystem elements to be ready for the first physics campaign. Many...

Commissioning and first tests of the MAGIC telescope (2004)

Baixeras, C., Bastieri, D., Bigongiari, C., Blanch, O., Blanchot, G., Bock, R., ...

Major Atmospheric Gamma Imaging Cherenkov telescope is starting its operations with a set of engineering runs to tune the telescope subsystem elements to be ready for the first physics campaign. Many...

Quasispecies and RNA viruses evolution (2001)

Domingo, E., Biebricher, C. K., Eigen, M., Holland, J. J.

Strong buffering capacity of insect cells. Implications for the baculovirus expression system. (1995)

Medina, M., Lopez-Rivas, A., Zuidema, D., Belsham, G.J., Domingo, E., Vlak, J.M.

Engineering and immunogenicity of foot-and-mouth disease virus procapsids produced in insect cells. (1995)

Belsham, G.J., Vlak, J.M., Domingo, E., Lombard, M.

Expression of foot-and-mouth disease virus empty capsid particles in insect cells. (1995)

Belsham, G.J., Vlak, J.M., Domingo, E., Lombard, M.

A novel approach for picornavirus vaccine development. (1994)

Zuidema, D., Saiz, J.-C., Cairo, J., Abrahams, C., Medina, M., Domingo, E., ...

Engineering and immunogenicity of foot and mouth disease virus procapsids produced in insect cells. (1994)

Belsham, G., Vlak, J.M., Domingo, E., Lombard, M.

Unprocessed foot-and-mouth disease virus capsid precursor displays discontinuous epitopes involved in viral neutralization. (1994)

Sáiz, J.-C., Cairo, J., Medina, M., Zuidema, D., Abrams, C., Belsham, G.J., ...

Exponential increases of RNA virus fitness during large population transmissions.

Novella, I S, Duarte, E A, Elena, S F, Moya, A, Domingo, E, Holland, J J

The great adaptability shown by RNA viruses is a consequence of their high mutation rates. Here we investigate the kinetics of virus fitness gains during repeated transfers of large virus populations...

Rapid cell variation can determine the establishment of a persistent viral infection.

Martín Hernández, A M, Carrillo, E C, Sevilla, N, Domingo, E

Evidence for a mechanism of initiation of viral persistence in which the cell, and not the virus, plays a critical role has been obtained using the important animal pathogen foot-and-mouth disease...

The red queen reigns in the kingdom of RNA viruses.

Clarke, D K, Duarte, E A, Elena, S F, Moya, A, Domingo, E, Holland, J

Two clonal populations of vesicular stomatitis virus of approximately equal relative fitness were mixed together and allowed to compete during many transfers in vitro as large virus populations....

Molecular indetermination in the transition to error catastrophe: Systematic elimination of lymphocytic choriomeningitis virus through mutagenesis does not correlate linearly with large increases in mutant spectrum complexity

Grande-Pérez, A., Sierra, S., Castro, M. G., Domingo, E., Lowenstein, P. R.

Studies with several RNA viruses have shown that enhanced mutagenesis resulted in decreases of infectivity or virus extinction, as predicted from virus entry into error catastrophe. Here we report...

Mispair extension fidelity of human immunodeficiency virus type 1 reverse transcriptases with amino acid substitutions affecting Tyr115.

Martín-Hernández, A M, Gutiérrez-Rivas, M, Domingo, E, Menéndez-Arias, L

The role of Tyr115 of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) in the mispair extension fidelity of DNA dependent DNA synthesis was analysed by using a series of 15 mutant...

Pol gene quasispecies of human immunodeficiency virus: mutations associated with drug resistance in virus from patients undergoing no drug therapy.

Nájera, I, Holguín, A, Quiñones-Mateu, M E, Muñoz-Fernández, M A, Nájera, R, López-Galíndez, C, ...

The nucleotide sequences of two pol gene regions (codons 41 to 108 and 181 to 219 of reverse transcriptase) of 60 human immunodeficiency virus type 1 genomes obtained directly from primary...

Size of genetic bottlenecks leading to virus fitness loss is determined by mean initial population fitness.

Novella, I S, Elena, S F, Moya, A, Domingo, E, Holland, J J

Genetic bottlenecks are important events in the genetic diversification of organisms and colonization of new ecological niches. Repeated bottlenecking of RNA viruses often leads to fitness losses due...

Extreme fitness differences in mammalian and insect hosts after continuous replication of vesicular stomatitis virus in sandfly cells.

Novella, I S, Clarke, D K, Quer, J, Duarte, E A, Lee, C H, Weaver, S C, ...

Continuous, persistent replication of a wild-type strain of vesicular stomatitis virus in cultured sandfly cells for 10 months profoundly decreased virus replicative fitness in mammalian cells and...

Identification of an essential region for internal initiation of translation in the aphthovirus internal ribosome entry site and implications for viral evolution.

Martínez-Salas, E, Regalado, M P, Domingo, E

Translation of aphthovirus RNA is initiated at an internal ribosome entry site (IRES) element, preceding the first functional AUG initiation codon. The effect of mutations at the base of domain 3 of...

Virulence as a positive trait in viral persistence.

Sáiz, J C, Domingo, E

A population replacement experiment has been devised to test the ability of a challenge virus to replace the resident virus in a persistently infected cell culture. BHK-21 cells persistently infected...

Large-population passages of vesicular stomatitis virus in interferon-treated cells select variants of only limited resistance.

Novella, I S, Cilnis, M, Elena, S F, Kohn, J, Moya, A, Domingo, E, ...

Vesicular stomatitis virus (VSV) populations were repeatedly passaged in L-929 cells treated with alpha interferon (IFN-alpha) at levels of 25 U/ml. This IFN-alpha concentration induced a 99.9%...

Evolution of a persistent aphthovirus in cytolytic infections: partial reversion of phenotypic traits accompanied by genetic diversification.

Sevilla, N, Domingo, E

Foot-and-mouth disease virus (FMDV) shows a dual potential to be cytolytic or to establish persistent infections in cell culture. FMDV R100, a virus rescued after 100 passages of carrier BHK-21 cells...

A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants.

Taboga, O, Tami, C, Carrillo, E, Núñez, J I, Rodríguez, A, Saíz, J C, ...

A large-scale vaccination experiment involving a total of 138 cattle was carried out to evaluate the potential of synthetic peptides as vaccines against foot-and-mouth disease. Four types of peptides...

Negative effects of chemical mutagenesis on the adaptive behavior of vesicular stomatitis virus.

Lee, C H, Gilbertson, D L, Novella, I S, Huerta, R, Domingo, E, Holland, J J

Changes in adaptability of vesicular stomatitis virus (VSV) upon treatment with chemical mutagens have been investigated. Results showed no improvement in virus viability or adaptability at any given...

Efficient neutralization of foot-and-mouth disease virus by monovalent antibody binding.

Verdaguer, N, Fita, I, Domingo, E, Mateu, M G

Neutralization of an aphthovirus by monovalent binding of an antibody is reported. Foot-and-mouth disease virus (FMDV) clone C-S8c1 was neutralized by monoclonal antibody (MAb) SD6, which was...

Subclonal components of consensus fitness in an RNA virus clone.

Duarte, E A, Novella, I S, Ledesma, S, Clarke, D K, Moya, A, Elena, S F, ...

Most RNA virus populations exhibit extremely high mutation frequencies which generate complex, genetically heterogeneous populations referred to as quasi-species. Previous work has shown that when a...

Unprocessed foot-and-mouth disease virus capsid precursor displays discontinuous epitopes involved in viral neutralization.

Sáiz, J C, Cairó, J, Medina, M, Zuidema, D, Abrams, C, Belsham, G J, ...

A foot-and-mouth disease virus (FMDV) cDNA cassette containing sequences encoding the capsid precursor P1, peptide 2A and a truncated 2B (abbreviated P1-2A) of type C FMDV, has been modified to...

Antigenic heterogeneity of a foot-and-mouth disease virus serotype in the field is mediated by very limited sequence variation at several antigenic sites.

Mateu, M G, Hernández, J, Martínez, M A, Feigelstock, D, Lea, S, Pérez, J J, ...

Antigenic variation in a major discontinuous site (site D) of foot-and-mouth disease virus (FMDV) of serotype C has been evaluated with neutralizing monoclonal antibodies. Isolates representing the...

Genetic bottlenecks and population passages cause profound fitness differences in RNA viruses.

Clarke, D K, Duarte, E A, Moya, A, Elena, S F, Domingo, E, Holland, J

Repeated clone-to-clone (genetic bottleneck) passages of an RNA phage and vesicular stomatitis virus have been shown previously to result in loss of fitness due to Muller's ratchet. We now...

Dilute passage promotes expression of genetic and phenotypic variants of human immunodeficiency virus type 1 in cell culture.

Sánchez-Palomino, S, Rojas, J M, Martínez, M A, Fenyö, E M, Nájera, R, Domingo, E, ...

We have studied the extent of genetic and phenotypic diversification of human immunodeficiency virus type 1 (HIV-1) upon 15 serial passages of clonal viral populations in MT-4 cell cultures. Several...

Many-trillionfold amplification of single RNA virus particles fails to overcome the Muller's ratchet effect.

Duarte, E A, Clarke, D K, Moya, A, Elena, S F, Domingo, E, Holland, J

We showed earlier that transfers of large populations of RNA viruses lead to fitness gains and that repeated genetic bottleneck transfers result in fitness losses due to Muller's ratchet. In the...

A single nucleotide substitution in the internal ribosome entry site of foot-and-mouth disease virus leads to enhanced cap-independent translation in vivo.

Martínez-Salas, E, Sáiz, J C, Dávila, M, Belsham, G J, Domingo, E

Mutants of foot-and-mouth disease virus (FMDV) with altered biological properties can be selected during the course of persistent infection of BHK-21 cells with FMDV C-S8c1 (J. C. de la Torre, E....

Distinct repertoire of antigenic variants of foot-and-mouth disease virus in the presence or absence of immune selection.

Borrego, B, Novella, I S, Giralt, E, Andreu, D, Domingo, E

Antigenic variants of foot-and-mouth disease virus (FMDV) were generated and frequently became dominant in clonal populations of FMDV (clone C-S8c1) grown in the absence of anti-FMDV antibodies. We...

Evolution of the capsid protein genes of foot-and-mouth disease virus: antigenic variation without accumulation of amino acid substitutions over six decades.

Martínez, M A, Dopazo, J, Hernández, J, Mateu, M G, Sobrino, F, Domingo, E, ...

The genetic diversification of foot-and-mouth disease virus (FMDV) of serotype C over a 6-decade period was studied by comparing nucleotide sequences of the capsid protein-coding regions of viruses...

Fitness alteration of foot-and-mouth disease virus mutants: measurement of adaptability of viral quasispecies.

Martínez, M A, Carrillo, C, González-Candelas, F, Moya, A, Domingo, E, Sobrino, F

We document the rapid alteration of fitness of two foot-and-mouth disease virus (FMDV) mutants resistant to a neutralizing monoclonal antibody. Both mutants showed a selective disadvantage in BHK-21...

Extensive cell heterogeneity during persistent infection with foot-and-mouth disease virus.

De La Torre, J C, Martínez-Salas, E, Díez, J, Domingo, E

Coevolution of viruses and the host cells occurred in BHK-21 cell cultures persistently infected with foot-and-mouth disease virus (FMDV) (J. C. de la Torre, E. Martínez-Salas, J. Diez, A....

Unique amino acid substitutions in the capsid proteins of foot-and-mouth disease virus from a persistent infection in cell culture.

Díez, J, Dávila, M, Escarmís, C, Mateu, M G, Dominguez, J, Pérez, J J, ...

Maintenance of a persistent foot-and-mouth disease virus (FMDV) infection in BHK-21 cells involves a coevolution of cells and virus (J. C. de la Torre, E. Martínez-Salas, J. Díez, A. Villaverde, F....

Resistance to foot-and-mouth disease virus mediated by trans-acting cellular products.

De La Torre, J C, De La Luna, S, Diez, J, Domingo, E

Upon serial passage of BHK-21 cells persistently infected with foot-and-mouth disease virus (FMDV) C-S8c1, cells with increased resistance to the virus were selected (J. C. de la Torre, E....

Virus mutation frequencies can be greatly underestimated by monoclonal antibody neutralization of virions.

Holland, J J, De La Torre, J C, Steinhauer, D A, Clarke, D, Duarte, E, Domingo, E

Monoclonal antibody-resistant mutants have been widely used to estimate virus mutation frequencies. We demonstrate that standard virion neutralization inevitably underestimates monoclonal...

VP1 of serotype C foot-and-mouth disease viruses: long-term conservation of sequences.

Piccone, M E, Kaplan, G, Giavedoni, L, Domingo, E, Palma, E L

The nucleotide sequences of the VP1-coding regions of several isolates of serotype C3 foot-and-mouth disease virus (FMDV) were determined. The deduced amino acid sequences were compared with those of...

Rapid selection of genetic and antigenic variants of foot-and-mouth disease virus during persistence in cattle.

Gebauer, F, De La Torre, J C, Gomes, I, Mateu, M G, Barahona, H, Tiraboschi, B, ...

Rapid evolution of foot-and-mouth disease virus (FMDV) is documented during persistent infections of cattle. The carrier state was established experimentally with plaque-purified FMDV of serotype C3....

Coevolution of cells and viruses in a persistent infection of foot-and-mouth disease virus in cell culture.

De La Torre, J C, Martínez-Salas, E, Diez, J, Villaverde, A, Gebauer, F, Rocha, E, ...

Virus and cells evolve during serial passage of cloned BHK-21 cells persistently infected with foot-and-mouth disease virus (FMDV). These carrier cells, termed C1-BHK-Rc1 (J.C. de la Torre, M....

Ribavirin cures cells of a persistent infection with foot-and-mouth disease virus in vitro.

De La Torre, J C, Alarcón, B, Martínez-Salas, E, Carrasco, L, Domingo, E

Ribavirin (1-beta-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide) eliminates foot-and-mouth disease virus from persistently infected cell cultures. The latter are 10-fold more sensitive to ribavirin...

Gene encoding capsid protein VP1 of foot-and-mouth disease virus: a quasispecies model of molecular evolution.

Dopazo, J, Sobrino, F, Palma, E L, Domingo, E, Moya, A

A phylogenetic tree relating the VP1 gene of 15 isolates of foot-and-mouth disease virus (FMDV) of serotypes A, C, and O has been constructed. The most parsimonious tree shows that FMDV subtypes and...

Implications of a quasispecies genome structure: effect of frequent, naturally occurring amino acid substitutions on the antigenicity of foot-and-mouth disease virus.

Mateu, M G, Martínez, M A, Rocha, E, Andreu, D, Parejo, J, Giralt, E, ...

We provide evidence that the quasispecies nature (extreme genetic heterogeneity) of foot-and-mouth disease virus is relevant to the virus evading an immune response. A monoclonal antibody...

A primer vector system that allows temperature dependent gene amplification and expression in mammalian cells: regulation of the influenza virus NS1 gene expression.

Portela, A, Melero, J A, Martínez, C, Domingo, E, Ortín, J

Influenza virus RNA segment 8 has been cloned into primer-vector pSLts1. This vector was designed to replicate in simian cells in a temperature dependent fashion by use of the SV40 tsA209 T-antigen...

Sequence variability in avocado sunblotch viroid (ASBV).

Pallás, V, García-Luque, I, Domingo, E, Flores, R

Structure of the major antigenic loop of foot-and-mouth disease virus complexed with a neutralizing antibody: direct involvement of the Arg-Gly-Asp motif in the interaction.

Verdaguer, N, Mateu, M G, Andreu, D, Giralt, E, Domingo, E, Fita, I

The crystal structure of a synthetic peptide representing the major antigenic loop of foot-and-mouth disease virus (FMDV), complexed with the Fab fragment of a neutralizing monoclonal antibody raised...

Rapid fitness losses in mammalian RNA virus clones due to Muller's ratchet.

Duarte, E, Clarke, D, Moya, A, Domingo, E, Holland, J

Muller's ratchet is an important concept in population genetics. It predicts that when mutation rates are high and a significant proportion of mutations are deleterious, a kind of irreversible...

Human immunodeficiency virus type 1 reverse transcriptase: role of Tyr115 in deoxynucleotide binding and misinsertion fidelity of DNA synthesis.

Martín-Hernández, A M, Domingo, E, Menéndez-Arias, L

Tyr115 is located in the vicinity of the polymerase catalytic site of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Site-directed mutagenesis was used to generate variant enzymes...

In vitro synthesis of full-length influenza virus complementary RNA.

Del Río, L, Martínez, C, Domingo, E, Ortín, J

Influenza virus-specific RNA has been synthesized in vitro, using cytoplasmic or microsomal fractions of influenza virus-infected MDCK cells. The RNA polymerase activity was stimulated 5-30 times by...

Structure of the complex of an Fab fragment of a neutralizing antibody with foot-and-mouth disease virus: positioning of a highly mobile antigenic loop.

Hewat, E A, Verdaguer, N, Fita, I, Blakemore, W, Brookes, S, King, A, ...

Data from cryo-electron microscopy and X-ray crystallography have been combined to study the interactions of foot-and-mouth disease virus serotype C (FMDV-C) with a strongly neutralizing monoclonal...

Evolution of Fitness in Experimental Populations of Vesicular Stomatitis Virus

Elena, S. F., Gonzalez-Candelas, F., Novella, I. S., Duarte, E. A., Clarke, D. K., Domingo, E., ...

The evolution of fitness in experimental clonal populations of vesicular stomatitis virus (VSV) has been compared under different genetic (fitness of initial clone) and demographic (population...