Expansion of quasispecies diversity but no evidence for adaptive evolution of SHIV during rapid serial transfers among seronegative macaques

Four successive, rapid serial passages of the nonpathogenic, CCR5-tropic simian-human immunodeficiency virus SHIV(SF162) in rhesus macaques resulted in an increase in acute plasma viremia with each passage and the emergence of a pathogenic isolate SHIV(SF162P3) in one of the passage three transfer a...

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Published in:Virology (New York, N.Y.) N.Y.), 2004-01, Vol.318 (1), p.267-279
Main Authors: Balfe, Peter, Shapiro, Sarah, Hsu, Mayla, Buckner, Clarisa, Harouse, Janet M, Cheng-Mayer, Cecilia
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Evolution, Molecular
Genetic Variation
HIV Envelope Protein gp120 - chemistry
HIV Envelope Protein gp120 - genetics
HIV Infections - virology
HIV Seronegativity
HIV-1 - classification
HIV-1 - genetics
HIV-1 - pathogenicity
Humans
Macaca mulatta
Macaca mulatta - virology
Molecular Sequence Data
Serial Passage
Simian Acquired Immunodeficiency Syndrome - virology
Simian Immunodeficiency Virus - classification
Simian Immunodeficiency Virus - genetics
Simian Immunodeficiency Virus - pathogenicity
simian-human immunodeficiency virus 162
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Summary:Four successive, rapid serial passages of the nonpathogenic, CCR5-tropic simian-human immunodeficiency virus SHIV(SF162) in rhesus macaques resulted in an increase in acute plasma viremia with each passage and the emergence of a pathogenic isolate SHIV(SF162P3) in one of the passage three transfer animals (macaque T353). To explore the mechanism(s) underlying increased virulence of SHIV(SF162) upon in vivo passage, the evolution of the HIV-1 envelope gene was characterized in plasma and PBMC samples obtained from animals before (week 1) and after (week 3) the time of virus transfer. We found no evidence in support of adaptive evolution of the HIV gp120 during rapid serial passage; however, the animals which later received passage virus had more diverse quasispecies. SHIV(SF162P3)-like gp120 sequences were first detected in macaque T353 at week 6, after seroconversion. These sequence changes increased in frequency and number at later time points. The first sequence change conferred neutralization escape but not an increase in viral infectivity that could account for the apparent increase in replicative capacity of the later passage viruses. Collectively, our data argue against any host-specific adaptation of the HIV-1 envelope gp120 as the basis for the generation of more aggressive SHIV variants during rapid serial transfers in seronegative macaques, and support the model of quasispecies diversity as a predictor of pathogenesis. Envelope sequence changes accumulate principally in response to immune pressure exerted by the host, generating viral variants that can persist in the presence of a strong host immune response.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2003.09.022