Concomitant emergence of the antisense protein gene of HIV-1 and of the pandemic.
Recent experiments provide sound arguments in favor of the in vivo expression of the AntiSense Protein (ASP) of HIV-1. This putative protein is encoded on the antisense strand of the provirus genome and entirely overlapped by the env gene with reading frame -2. The existence of ASP was suggested in 1988, but is still controversial, and its function has yet to be determined. We used a large dataset of ∼23,000 HIV-1 and SIV sequences to study the origin, evolution, and conservation of the asp gene. We found that the ASP ORF is specific to group M of HIV-1, which is responsible for the human pandemic. Moreover, the correlation between the presence of asp and the prevalence of HIV-1 groups and M subtypes appeared to be statistically significant. We then looked for evidence of selection pressure acting on asp Using computer simulations, we showed that the conservation of the ASP ORF in the group M could not be due to chance. Standard methods were ineffective in disentangling the two selection pressures imposed by both the Env and ASP proteins-an expected outcome with overlaps in frame -2. We thus developed a method based on careful evolutionary analysis of the presence/absence of stop codons, revealing that ASP does impose significant selection pressure. All of these results support the idea that asp is the 10th gene of HIV-1 group M and indicate a correlation with the spread of the pandemic.
Institut de Biologie Computationnelle, Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM)-UMR 5506 CNRS and Université de Montpellier, 34095 Montpellier, France; Centre d'Études d'Agents Pathogènes et Biotechologies pour la Santé (CPBS)-FRE 3689 CNRS and Université de Montpellier, 34293 Montpellier, France; olivier.gascuel@pasteur.fr antoine.gross@cpbs.cnrs.fr elodie.cassan@lirmm.fr.
Elodie
E
Cassan
Institut de Biologie Computationnelle, Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM)-UMR 5506 CNRS and Université de Montpellier, 34095 Montpellier, France.
Anne-Muriel
AM
Arigon-Chifolleau
Centre d'Études d'Agents Pathogènes et Biotechologies pour la Santé (CPBS)-FRE 3689 CNRS and Université de Montpellier, 34293 Montpellier, France.
Jean-Michel
JM
Mesnard
Centre d'Études d'Agents Pathogènes et Biotechologies pour la Santé (CPBS)-FRE 3689 CNRS and Université de Montpellier, 34293 Montpellier, France; olivier.gascuel@pasteur.fr antoine.gross@cpbs.cnrs.fr elodie.cassan@lirmm.fr.
Antoine
A
Gross
Institut de Biologie Computationnelle, Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM)-UMR 5506 CNRS and Université de Montpellier, 34095 Montpellier, France; Unité Bioinformatique Evolutive, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI)-USR 3756 CNRS and Institut Pasteur, 75015 Paris, France olivier.gascuel@pasteur.fr antoine.gross@cpbs.cnrs.fr elodie.cassan@lirmm.fr.
Olivier
O
Gascuel
D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D016679:Genome, Viral; D015658:HIV Infections / Q000453:epidemiology* / Q000235:genetics / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D058873:Pandemics; D010802:Phylogeny; D016364:Reading Frames / Q000235:genetics; D012641:Selection, Genetic; D014764:Viral Proteins / Q000235:genetics*
D014764:Viral Proteins
HIV-1; asp and env genes; overlapping genes; phylogenetic analyses; selection pressure
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