20962091
not annotated - annotated - LINNAEUS only
Macaque long-term nonprogressors resist superinfection with multiple CD8+ T cell escape variants of simian immunodeficiency virus.
Human immunodeficiency virus (HIV)-positive individuals can be superinfected with different virus strains. Individuals who control an initial HIV infection are therefore still at risk for subsequent infection with divergent viruses, but the barriers to such superinfection remain unclear. Here we tested long-term nonprogressors' (LTNPs') susceptibility to superinfection using Indian rhesus macaques that express the major histocompatibility complex class I (MHC-I) allele Mamu-B 17, which is associated with control of the pathogenic AIDS virus SIVmac239. The Mamu-B 17-restricted CD8(+) T cell repertoire is focused almost entirely on 5 epitopes. We engineered a series of SIVmac239 variants bearing mutations in 3, 4, or all 5 of these epitopes and used them to serially challenge 2 Mamu-B 17-positive LTNPs. None of the escape variants caused breakthrough replication in LTNPs, although they readily infected Mamu-B 17-negative naive macaques. In vitro competing coculture assays and examination of viral evolution in hosts lacking Mamu-B 17 suggested that the mutant viruses had negligible defects in replicative fitness. Both LTNPs maintained robust immune responses, including simian immunodeficiency virus (SIV)-specific CD8(+) and CD4(+) T cells and neutralizing antibodies. Our results suggest that escape mutations in epitopes bound by "protective" MHC-I molecules may not be sufficient to establish superinfection in LTNPs.
Ann file
T1 Species 100 129 simian immunodeficiency virus
N1 Reference T1 Taxonomy:11723
T2 Species 133 161 Human immunodeficiency virus
N2 Reference T2 Taxonomy:12721
T3 Species 163 166 HIV
N3 Reference T3 Taxonomy:12721
T4 Species 275 278 HIV
N4 Reference T4 Taxonomy:12721
T5 Species 511 533 Indian rhesus macaques
N5 Reference T5 Taxonomy:9544
T6 Species 680 689 SIVmac239
N6 Reference T6 Taxonomy:11723
T7 Species 1318 1347 simian immunodeficiency virus
N7 Reference T7 Taxonomy:11723
T8 Species 1349 1352 SIV
N8 Reference T8 Taxonomy:11723
T9 Species 809 818 SIVmac239
N9 Reference T9 Taxonomy:11723
#2 AnnotatorNotes T9 TODO check