A novel protective MHC-I haplotype not associated with dominant Gag-specific CD8+ T-cell responses in SIVmac239 infection of Burmese rhesus macaques.
Several major histocompatibility complex class I (MHC-I) alleles are associated with lower viral loads and slower disease progression in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. Immune-correlates analyses in these MHC-I-related HIV/SIV controllers would lead to elucidation of the mechanism for viral control. Viral control associated with some protective MHC-I alleles is attributed to CD8+ T-cell responses targeting Gag epitopes. We have been trying to know the mechanism of SIV control in multiple groups of Burmese rhesus macaques sharing MHC-I genotypes at the haplotype level. Here, we found a protective MHC-I haplotype, 90-010-Id (D), which is not associated with dominant Gag-specific CD8+ T-cell responses. Viral loads in five D+ animals became significantly lower than those in our previous cohorts after 6 months. Most D+ animals showed predominant Nef-specific but not Gag-specific CD8+ T-cell responses after SIV challenge. Further analyses suggested two Nef-epitope-specific CD8+ T-cell responses exerting strong suppressive pressure on SIV replication. Another set of five D+ animals that received a prophylactic vaccine using a Gag-expressing Sendai virus vector showed significantly reduced viral loads compared to unvaccinated D+ animals at 3 months, suggesting rapid SIV control by Gag-specific CD8+ T-cell responses in addition to Nef-specific ones. These results present a pattern of SIV control with involvement of non-Gag antigen-specific CD8+ T-cell responses.
AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Naofumi
N
Takahashi
Takushi
T
Nomura
Yusuke
Y
Takahara
Hiroyuki
H
Yamamoto
Teiichiro
T
Shiino
Akiko
A
Takeda
Makoto
M
Inoue
Akihiro
A
Iida
Hiroto
H
Hara
Tsugumine
T
Shu
Mamoru
M
Hasegawa
Hiromi
H
Sakawaki
Tomoyuki
T
Miura
Tatsuhiko
T
Igarashi
Yoshio
Y
Koyanagi
Taeko K
TK
Naruse
Akinori
A
Kimura
Tetsuro
T
Matano
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016679:Genome, Viral / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D008253:Macaca mulatta; D008285:Major Histocompatibility Complex / Q000235:genetics*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity