Rev activity determines sensitivity of HIV-1-infected primary T cells to CTL killing.
The HIV Nef protein is thought to promote HIV immune evasion by downmodulating MHC-I and protecting infected cells from CTL killing. In addition, we demonstrated that Rev, an HIV regulatory protein needed for expression of the HIV late genes, can influence CTL killing. When Rev activity level was reduced by virtue of amino acid alterations in the Rev protein sequence, infected cells were more resistant to anti-Gag and anti-Env CTL killing. A screen of primary viral isolates revealed that viruses derived from asymptomatic, infected people had lower Rev activity, lower Gag levels, and greater resistance to anti-Gag CTL killing. Thus, rev alleles with low activity may have a selective advantage in infected people with effective immune responses.
Bobbitt
Kevin R
KR
Department of Internal Medicine, The University of Michigan, Ann Arbor, MI 48109, USA.
Addo
Marylyn M
MM
Altfeld
Marcus
M
Filzen
Tracey
T
Onafuwa
Adewunmi A
AA
Walker
Bruce D
BD
Collins
Kathleen L
KL
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004279:DNA, Viral / Q000235:genetics; D015694:Gene Products, rev / Q000235:genetics / Q000378:metabolism*; D015757:Genes, rev; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D018448:Models, Immunological; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054321:rev Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015694:Gene Products, rev; D054321:rev Gene Products, Human Immunodeficiency Virus