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In this review, the roles of Fc-gamma receptor polymorphisms are discussed in regards to HIV-1 vaccine efficacy, HIV acquisition, and disease progression. In addition, the significance of the neonatal immunoglobulin G (IgG) Fc receptor and potential effects of the aggregated immunoglobulin A Fc receptor (FcalphaR) are addressed.Fc receptors undoubtedly play an important role in antibody-mediated action in HIV infection and vaccines. Several studies have determined an association between polymorphic variants of Fc-gamma-RIIA and Fc-gamma-RIIIA in the acquisition and progression of HIV-1 infection, and in responses to vaccination regimens. A rather complex relationship exists between the relative affinity of these molecules and their impact on HIV disease acquisition and progression and HIV vaccine efficacy.The discrepancies between different investigations of the role of Fc receptor polymorphisms appear to derive from the complex nature of the Fc receptor functions, including factors such as epistatic interactions and the race, sex, age, and relative risk behavior of the investigated individuals. Furthermore, Fc receptors in nonhuman primates (NHPs), the key model to study an AIDS-like disease in an animal model, appear to be even more diverse than in humans, and the function of these proteins has not been extensively explored. Given the critical role of Fc receptors in antibody-mediated function in humans and NHP, more investigations are needed to fully understand and exploit these functions for vaccine design.

Soon after the discovery of HIV-infected humans, rhesus macaques in a colony at the New England Primate Research Center showed similar signs of a progressive immune suppression. The discovery of the simian immunodeficiency virus (SIV)-associated disease opened the door to study an AIDS-like illness in nonhuman primates (NHP). Even after 3 decades, this animal model remains an invaluable tool to provide a greater insight into HIV immunopathogenesis. In this review, recent progress in deciphering pathways of immunopathogenesis in SIV-infected NHP is discussed.The immense diversity of mutations in SIV stocks prepared at different laboratories has recently been realized. The massive expansion of the enteric virome is a key finding in SIV-induced immunopathogenesis. Defining the function of host restriction factors, like the recently discovered SAMHD1, helps to evaluate the impact of the innate immune responses on virus replication. Utilization of pyrosequencing and defining molecular mechanisms of major histocompatibility complex (MHC) class I restriction helps to understand how the virus evades CD8 T-cell responses. The definition of MHC class I molecules in different NHP species provides new animal models to study SIV immunopathogenesis. T follicular helper cells have gained major interest in characterizing humoral immune responses in SIV infection and AIDS vaccine strategies. The ability of natural hosts to remain disease-free despite ongoing replication of SIV is continuing to puzzle the field.The HIV research field continues to realize the immense complexity of the host virus interaction. NHP present an invaluable tool to make progress towards an effective AIDS vaccine.