Natural selection and the organ-specific differentiation of HIV-1 V3 hypervariable region.
The existence of organ-specific HIV-1 populations within infected hosts has been studied for many years; nonetheless results reported by different authors are somewhat discrepant. To tackle this problem, we used a population genetics approach to analyze previously published data from the V3 hypervariable region of the envelope env gene. Our results are compatible with a population subdivision by organs in 95% of individuals analyzed at autopsy. In addition, populations infecting the nervous system and testicles clearly appear as differentiated subsets of the so-called macrophage-tropic variants. Liver and kidney may harbor differentiated populations as well. Although it is widely accepted that organ compartmentalization arises as a consequence of different selective pressures imposed by different organs, a definitive demonstration has not yet been provided. Our analysis of the pattern of synonymous and nonsynonymous nucleotide substitutions provides evidence supporting this hypothesis, without discarding the role of other evolutionary processes. In contrast, positive selection does not seem to be the mechanism responsible for the evolution of patient-specific sequences.
Sanjuán
Rafael
R
Institut Cavanilles de Biodiversitat i Biologia Evolutiva and Departament de Genètica, Universitat de València, 46071 València, Spain.
Codoñer
Francisco M
FM
Moya
Andrés
A
Elena
Santiago F
SF
D000704:Analysis of Variance; D001483:Base Sequence; D016000:Cluster Analysis; D030561:Databases, Nucleic Acid; D019143:Evolution, Molecular; D005828:Genetics, Population; D006678:HIV / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D009928:Organ Specificity / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics*; D012641:Selection, Genetic; D016415:Sequence Alignment
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments