Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants.
Viral escape from cytotoxic T lymphocytes (CTLs) can undermine immune control of human immunodeficiency virus 1. It is therefore important to assess the stability of viral mutations in CTL epitopes after transmission to naive hosts. Here we demonstrate the persistence of mutations in a dominant CTL epitope after transmission of simian immunodeficiency virus variants to major histocompatibility complex-matched rhesus monkeys. Transient reversions to wild-type sequences occurred and elicited CTLs specific for the wild-type epitope, resulting in immunological pressure that rapidly reselected the mutant viruses. These data suggest that mutations in dominant human immunodeficiency virus 1 CTL epitopes may accumulate in human populations with limited major histocompatibility complex heterogeneity by a mechanism involving dynamic CTL control of transiently reverted wild-type virus.
Barouch
Dan H
DH
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. dbarouch@bidmc.harvard.edu <dbarouch@bidmc.harvard.edu>
Powers
Jennifer
J
Truitt
Diana M
DM
Kishko
Michael G
MG
Arthur
Janelle C
JC
Peyerl
Fred W
FW
Kuroda
Marcelo J
MJ
Gorgone
Darci A
DA
Lifton
Michelle A
MA
Lord
Carol I
CI
Hirsch
Vanessa M
VM
Montefiori
David C
DC
Carville
Angela
A
Mansfield
Keith G
KG
Kunstman
Kevin J
KJ
Wolinsky
Steven M
SM
Letvin
Norman L
NL
D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D008253:Macaca mulatta; D008285:Major Histocompatibility Complex / Q000276:immunology; D009154:Mutation; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes