Continuous viral escape and selection by autologous neutralizing antibodies in drug-naive human immunodeficiency virus controllers.
We assessed differences in the character and specificity of autologous neutralizing antibodies (ANAbs) against individual viral variants of the quasispecies in a cohort of drug-naïve subjects with long-term controlled human immunodeficiency virus type 1 (HIV-1) infection and moderate levels of broad heterologous neutralizing antibodies (HNAb). Functional plasma virus showed continuous env evolution despite a short time frame and low levels of viral replication. Neutralization-sensitive variants dominated in subjects with intermittent viral blips, while neutralization-resistant variants predominated in elite controllers. By sequence analysis of this panel of autologous variants with various sensitivities to neutralization, we identified more than 30 residues in envelope proteins (Env) associated with resistance or sensitivity to ANAbs. The appearance of new sensitive variants is consistent with a model of continuous selection and turnover. Strong ANAb responses directed against autologous Env variants are present in long-term chronically infected individuals, suggesting a role for these responses in contributing to the durable control of HIV replication.
Mahalanabis
Madhumita
M
Department of Microbiology,University of Washington, Seattle, Washington 98195, USA.
Jayaraman
Pushpa
P
Miura
Toshiyuki
T
Pereyra
Florencia
F
Chester
E Michael
EM
Richardson
Barbra
B
Walker
Bruce
B
Haigwood
Nancy L
NL
D015331:Cohort Studies; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000276:immunology; D009500:Neutralization Tests; D010802:Phylogeny; D010949:Plasma / Q000821:virology; D020836:Protein Structure, Quaternary; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus