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Host genetic polymorphisms associated with innate immune factors and HIV-1

Sobieszczyk, Magdalena E.a; Lingappa, Jairam R.b,d; McElrath, M. Julianab,c

doi: 10.1097/COH.0b013e3283497155
Innate immunity: Edited by William A. Paxton and Teunis B.H. Geijtenbeek

Purpose of review: Our understanding of the early events in HIV-1 infection continues to grow, along with the heightened recognition of the important contribution that innate immunity plays in response to HIV-1. Here, we review the epidemiological and functional studies of genetic polymorphisms associated with innate immune factors that are believed to modulate host responses, focusing specifically on recent findings related to Toll-like receptor, cytokine, host restriction and KIR genes and their activities.

Recent findings: A growing number of genomic studies have described polymorphisms in innate immune genes that are associated with early postseroconversion events, including TLR4, TLR9, IRF-3, TRIM5α and the ABOBEC3 gene family. Genetic and functional data confirm the importance of KIR–HLA interactions and provide new understanding of the role of innate restriction factors in resistance to HIV-1 and disease progression.

Summary: Single-gene, genome-wide association and expression studies have permitted the identification of innate immune genes and their variants that contribute to protection from disease progression. Characterization of the pathogen–innate immune system interactions and discovery of new and rare host genetic variants that account for a portion of the observed variance in the HIV-1 phenotype is critical to gain new insights into promising treatment and prevention strategies.

aDepartment of Medicine, Columbia University College of Physicians and Surgeons, New York, New York

bDepartments of Global Health and Medicine, University of Washington

cVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center

dDepartment of Pediatrics, University of Washington, Seattle, Washington, USA

Correspondence to M. Juliana McElrath, MD, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N D3-100, PO Box 19024, Seattle, WA 98109-1024, USA Tel: +1 206 667 6704; e-mail: jmcelrat@fhcrc.org

© 2011 Lippincott Williams & Wilkins, Inc.