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Host genetic determinants of HIV pathogenesis: an immunologic perspective
Peter W Hunt1, Mary Carrington
1San Francisco General Hospital AIDS Division, University of California, San Francisco, California 94110, USA. phunt@php.ucsf.edu
Current Opinion in HIV and AIDS
|April 18, 2009
Summary
Recent studies reveal host genetic factors influencing HIV pathogenesis. Understanding these genetic determinants, including CCR5 variations, offers new targets for HIV vaccines and immune-based therapies.
Area of Science:
- Immunology
- Genetics
- Virology
Background:
- HIV pathogenesis is complex, involving interactions between the virus and the host immune system.
- Host genetic factors play a significant role in determining individual susceptibility and disease progression.
- Recent advances have shed light on the specific genetic determinants involved.
Purpose of the Study:
- To review recent findings on host genetic determinants of HIV pathogenesis.
- To provide a framework for understanding these genetic influences on HIV immunopathogenesis.
- To identify potential therapeutic and vaccine targets based on host genetics.
Main Methods:
- Genome-wide association studies (GWAS) of host determinants.
- Analysis of killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) allele interactions.
- Evaluation of genetic variations in CCR5 and its ligands.
Main Results:
- Both adaptive and innate immune responses are implicated in controlling HIV replication.
- Genetic variations in CCR5 are strongly linked to reduced HIV susceptibility and slower disease progression.
- These CCR5 variations appear to act independently of viral replication rates.
Conclusions:
- Host factors controlling HIV replication are key targets for vaccine development.
- Factors associated with delayed progression offer targets for novel immune-based HIV therapies.
- CCR5 inhibitors may have a role as immune-based treatments for HIV disease.
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