Abstract
Fc receptor (FcR) genes collectively have copy number and allelic polymorphisms that have been implicated in multiple inflammatory and autoimmune diseases. This variation might also be involved in etiology of infectious diseases. The protective role of Fc-mediated antibody-function in HIV-1 immunity has led to the investigation of specific polymorphisms in FcR genes on acquisition, disease progression, and vaccine efficacy in natural history cohorts. The purpose of this review is not only to explore these known HIV-1 host genetic associations, but also to re-evaluate them in the context of genome-wide data. In the current era of effective anti-retroviral therapy, the potential impact of such variation on post-treatment cohorts cannot go unheeded and is discussed here in the light of current findings. Specific polymorphisms associating with HIV-1 pathogenesis have previously been genotyped by assays that captured only the single-nucleotide polymorphism (SNP) of interest without relative information of neighboring variants. With recent technological advances, variation within these genes can now be characterized using next-generation sequencing, allowing precise annotation of the whole chromosomal region. We herein also discuss updates in the annotation of common FcR variants that have been previously associated with HIV-1 pathogenesis.
Highlights
Fc receptors comprise a class of cell surface receptors expressed on various hematopoietic cells that bind to the Fc portion of antibodies to form immune complexes and recruit the complement and/or effector system to defend the body against pathogens
There is evidence that the neonatal Fc receptor (FcRn), an MHC class I-related molecule expressed on many cells, functions in HIV-1 vaccination and infection [7, 8], no significant genetic variation has been identified for this locus, and we have not included it in this review
AOnly single-nucleotide polymorphism (SNP) variants with a MAF of >0.01 are shown. bThe status of FCGR2C has been recently changed from gene to pseudogene in genbank. cNo unique genome reference sequence has been defined for FCAR in genbank at this point. drs1801274 and rs396991 have been commonly referenced in the literature as FCGR2A-131R/H and FCGR3A-158F/V, respectively
Summary
Fc receptor (FcR) genes collectively have copy number and allelic polymorphisms that have been implicated in multiple inflammatory and autoimmune diseases. This variation might be involved in etiology of infectious diseases. The protective role of Fc-mediated antibody-function in HIV-1 immunity has led to the investigation of specific polymorphisms in FcR genes on acquisition, disease progression, and vaccine efficacy in natural history cohorts. Specific polymorphisms associating with HIV-1 pathogenesis have previously been genotyped by assays that captured only the single-nucleotide polymorphism (SNP) of interest without relative information of neighboring variants. We discuss updates in the annotation of common FcR variants that have been previously associated with HIV-1 pathogenesis
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