Impact of pre-adapted HIV transmission.

2016 | Nat Med

Program(s): Laboratory |

Abstract:

Human leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4(+) T cell decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to the expression of certain HLA alleles. Thus, viral pre-adaptation exploits 'holes' in the immune response. Accounting for these holes may be key for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies that require broad CTL responses to achieve successful eradication of HIV reservoirs.

Text or Node

Carlson JM

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© Copyright BC Centre for Excellence in HIV/AIDS
St. Paul's Hospital 608–1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6
Tel: 604-806-8477 | Fax: 604-806-9044
General inquiries: info@bccfe.ca
Media inquiries: communications@bccfe.ca
(Please do not use any of these email addresses to send personal information or book an appointment. To book appointments or contact the H2H clinic, please call 604-416-1517 or fax: 604-564-4893. Do not send your or your client's personal information via email.)

© Copyright BC Centre for Excellence in HIV/AIDS
St. Paul's Hospital 608–1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6
Tel: 604-806-8477 | Fax: 604-806-9044
General inquiries: info@bccfe.ca
Media inquiries: communications@bccfe.ca
(Please do not use any of these email addresses to send personal information or book an appointment. To book appointments or contact the H2H clinic, please call 604-416-1517 or fax: 604-564-4893. Do not send your or your client's personal information via email.)

Our work serves clients and communities across British Columbia on lands and waters cared for and nurtured by the many distinct First Nations across the province. The BC-CfE humbly and gratefully acknowledge the stewards of these lands, particularly the xʷməθkʷəy̓əm (Musqueam), Sḵwx̱wú7mesh (Squamish), and səl̓ílwətaʔ (Tsleil-Waututh) on whose unceded, traditional and ancestral territories our offices are located.