Are Fc Gamma Receptor Polymorphisms Important in HIV-1 Infection Outcomes and Latent Reservoir Size?

Helena Lamptey,Bright Adu,Evelyn Y. Bonney,George B. Kyei

doi:10.3389/fimmu.2021.656894

Abstract

Fc gamma receptors (FcγR) are cell surface glycoproteins which trigger specific effector-cell responses when cross-linked with the Fc portions of immunoglobulin (IgG) antibodies. During HIV-1 infection, the course of disease progression, ART response, and viral reservoir size vary in different individuals. Several factors may account for these differences; however, Fc gamma receptor gene polymorphisms, which influence receptor binding to IgG antibodies, are likely to play a key role. FcγRIIa (CD32) was recently reported as a potential marker for latent HIV reservoir, however, this assertion is still inconclusive. Whether FcγR polymorphisms influence the size of the viral reservoir, remains an important question in HIV cure studies. In addition, potential cure or viral suppression methods such as broadly neutralizing antibody (bNAbs) may depend on FcγRs to control the virus. Here, we discuss the current evidence on the potential role played by FcγR polymorphisms in HIV-1 infection, treatment and vaccine trial outcomes. Importantly, we highlight contrasting findings that may be due to multiple factors and the relatively limited data from African populations. We recommend further studies especially in sub-Saharan Africa to confirm the role of FcγRIIa in the establishment of latent reservoir and to determine their influence in therapies involving bNAbs.

Highlights

An estimated 37.9 million people are infected with the human immunodeficiency virus (HIV)
We summarize current knowledge on the role of Fc gamma receptor (FcgR) gene polymorphisms and HIV-1 infection, in relation to Antiretroviral therapy (ART) outcomes and control of the viral reservoir
Studies have shown variation in Fc glycosylation of HIV-specific antibodies in HIV-1 infected patients and vaccine recipients, an indication that it regulates antibody and FcgR interaction [76, 77]. These findings suggest possible mechanisms associated with increased risk of HIV-1infection in HVTN-505 vaccine among individuals carrying certain FcgRIIc genotypes, the same effect could not be established among recipients of the RV144 vaccine

Summary

INTRODUCTION

An estimated 37.9 million people are infected with the human immunodeficiency virus (HIV). A study that used samples from the European Multicenter AIDS Cohort Study (MACS), found an association between FcgRIIa-131R/R genotype and a faster rate of CD4+ T cell decline and disease progression compared to individuals with the R131H or H131H genotypes [12] This may be due to the weaker binding of the 131R/R receptor to IgG2 and IgG3 immune complexes. The expression of FcgRIIa on immune cells leads to the activation and production of proinflammatory cytokines, an indication that FcgRIIa-mediated T-cell activation would be more efficient in individuals carrying the FcgRIIa-H/H genotype [59, 60] This suggests that FcgRIIa polymorphism may indirectly influence CD4+ T cell function, and subsequent disease progression through its effect on immune complex internalization by monocytes and dendritic cells leading to their activation [59, 60]. A marker for T cell activation, but not for HIV-1 reservoir

58 HIV-1 infected FcgRIIa and FcgRIIIa

Findings

PERSPECTIVES AND CONCLUSION