Journal
CELL HOST & MICROBE
Volume 19, Issue 5, Pages 686-695Publisher
CELL PRESS
DOI: 10.1016/j.chom.2016.04.005
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Funding
- Frederick National Laboratory for Cancer Research [HHSN261200800001E]
- Center for HIV/AIDS Vaccine Immunology [U19 AI067854]
- Intramural Research Program of the NIH, Frederick National Laboratory, Center for Cancer Research
- Michael Smith Foundation for Health Research
- Medical Research Council [G0801937] Funding Source: researchfish
- MRC [G0801937] Funding Source: UKRI
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Many pathogens evade cytotoxic T lymphocytes (CTLs) by downregulating HLA molecules on infected cells, but the loss of HLA can trigger NK cell-mediated lysis. HIV-1 is thought to subvert CTLs while preserving NK cell inhibition by Nef-mediated downregulation of HLA-A and -B but not HLA-C molecules. We find that HLA-C is downregulated by most primary HIV-1 clones, including transmitted founder viruses, in contrast to the laboratory-adapted NL4-3 virus. HLA-C reduction ismediated by viral Vpu and reduces the ability of HLA-C restricted CTLs to suppress viral replication in CD4+ cells in vitro. HLA-A/B are unaffected by Vpu, and primary HIV-1 clones vary in their ability to downregulate HLA-C, possibly in response to whether CTLs or NK cells dominate immune pressure through HLA-C. HIV-2 also suppresses HLA-C expression through distinct mechanisms, underscoring the immune pressure HLA-C exerts on HIV. This viral immune evasion casts new light on the roles of CTLs and NK cells in immune responses against HIV.
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