Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection.
Cytotoxic T-lymphocyte (CTL) responses peak coincident with the decline in acute HIV viremia. Despite two reports of CTL-resistant HIV variants emerging during acute infection, the contribution of acute CTL escape to HIV pathogenesis remains unclear. Difficulties inherent in studying acute HIV infection can be overcome by modeling virus-host interactions in SIV-infected rhesus macaques. We sequenced 21 complete simian immunodeficiency virus (SIV)mac239 genomes at four weeks post-infection to determine the extent of acute CTL escape. Here we show that viruses from 19 of 21 macaques escaped from CTLs during acute infection and that these escape-selecting CTLs were responsive to lower concentrations of peptide than other SIV-specific CTLs. Interestingly, CTLs that require low peptide concentrations for stimulation (high 'functional avidity') are particularly effective at controlling other viral infections. Our results suggest that acute viral escape from CTLs is a hallmark of SIV infection and that CTLs with high functional avidity can rapidly select for escape variants.
O'Connor
David H
DH
Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Allen
Todd M
TM
Vogel
Thorsten U
TU
Jing
Peicheng
P
DeSouza
Ivan P
IP
Dodds
Elizabeth
E
Dunphy
Edward J
EJ
Melsaether
Cheri
C
Mothé
Bianca
B
Yamamoto
Hiroshi
H
Horton
Helen
H
Wilson
Nancy
N
Hughes
Austin L
AL
Watkins
David I
DI
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D001483:Base Sequence; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D016368:Frameshift Mutation; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D016415:Sequence Alignment; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D012367:RNA, Viral; D014764:Viral Proteins