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.