Balancing reversion of cytotoxic T-lymphocyte and neutralizing antibody escape mutations within human immunodeficiency virus type 1 Env upon transmission.
Human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) is subject to both neutralizing antibody (NAb) and CD8 T-cell (cytotoxic T-lymphocyte [CTL]) immune pressure. We studied the reversion of the Env CTL escape mutant virus to the wild type and the relationship between the reversion of CTL mutations with N-linked glycosylation site (NLGS)-driven NAb escape in pigtailed macaques. Env CTL mutations either did not revert to the wild type or only transiently reverted 5 to 7 weeks after infection. The CTL escape mutant reversion was coincident, for the same viral clones, with the loss of NLGS mutations. At one site studied, both CTL and NLGS mutations were needed to confer NAb escape. We conclude that CTL and NAb escape within Env can be tightly linked, suggesting opportunities to induce effective multicomponent anti-Env immunity.
Peut
Viv
V
Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
Campbell
Shahan
S
Gaeguta
Adriana
A
Center
Rob J
RJ
Wilson
Kim
K
Alcantara
Sheilajen
S
Fernandez
Caroline S
CS
Purcell
Damian F J
DF
Kent
Stephen J
SJ
D000220:Adaptation, Biological; D000818:Animals; D006031:Glycosylation; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008251:Macaca; D020125:Mutation, Missense; D009500:Neutralization Tests; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission* / Q000821:virology*; D015302:Simian Immunodeficiency Virus; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*
D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus