Genetic and Immunological Factors Involved in Natural Resistance to HIV-1 Infection

Abstract

Infection with Human immunodeficiency virus type-1 (HIV-1) induces severe alterations of the immune system leading to an increased susceptibility to opportunistic infections and malignancies. However, exposure to the virus does not always results in infection. Indeed, there exist individuals who have been repeatedly exposed to HIV-1 but do not exhibit clinical or serological evidence of infection, known as exposed seronegative individuals. Many studies have focused on the different mechanisms involved in natural resistance to HIV-1 infection, and have reported several factors associated with this phenomenon, including the presence of genetic polymorphisms in the viral coreceptors, innate and adaptive immune cells with particular phenotypic and functional features, and molecules such as antibodies and soluble factors that play an important role in defense against infection by HIV-1. The study of these factors could be the key for controlling this viral infection. This review summarizes the main mechanisms involved in resistance to HIV-1 infection.

Virus–host interaction in feline immunodeficiency virus (FIV) infection

“…Major efforts have been devoted in recent years to the discovery of novel alternatives to the treatment, and perhaps even cure, of HIV infection. For that purpose, many studies seek to understand the factors that are involved in the natural resistance to HIV-1 infection that occurs in some individuals who, despite a history of frequent (sexual, parenteral, or vertical) exposure to the virus, do not exhibit any serologic evidence of infection or any sign of immunodeficiency [56]. These high-risk exposed but seronegative (ESN) individuals seem to have genetic and immunological factors that reduce their susceptibility to infection, although a single factor individually may not account for this characteristic [57].…”

“…Amongst the genetic factors involved in the slow progression of AIDS and resistance to HIV infection, the following have been identified: alleles of human leucocyte antigen (HLA), the presence of activators or the absence of inhibitors of the genes encoding KIR (killer immunoglobulin-like receptor) molecules, a genetic polymorphism of the chemokines RANTES (regulated on activation normal T-cell expressed and secreted), macrophage inflammatory protein (MIP)-1␣, and MIP-1␤ and their receptors [56,57]. Amongst these alterations, the deletion of 32 base pairs of the gene encoding the CCR5 receptor (CCR5 32) is strongly correlated with resistance to HIV infection [58].…”

“…The host's innate immunity contributes to the protection against HIV infection mainly through the activity of NK cells and a large production of IFN␥. In addition, an increased production of ␤-chemokines (e.g., CC chemokine ligand (CCL)2, CCL3 (MIP-1␣), CCL4 (MIP-1␤), CCL5 (RANTES), and CCL11), ␣-chemokines (stromal cell-derived factor-1 (SDF-1)), peroxiredoxin II, CD8 + cell antiviral factor (CAF), NK cell stimulatory factor B, IL-22 (cytokine involved in the production of acute-phase proteins), defensins, and ribonucleases have been associated with protective effects [revised in 56,57]. The innate immune response mediated by cellular restriction factors, such as APOBEC3 (apolipoprotein B mRNA-editing catalytic polypeptide 3), Trim5␣ (tripartite motif protein), and tetherin, inhibits the viral replication of retroviruses and thus blocks the establishment of infection after the virus has entered the host cell [57,58].…”

“…According to recent observations in humans, exposure to HIV increases the expression of APOBEC3G, and ESN individuals exhibit a higher expression of this protein compared with non-exposed individuals. In addition, APOBEC3G reduces the susceptibility to HIV infection in vitro [56][57][58]. In cats, the action of APOBEC3G was investigated with three exogenous feline retroviruses: FIV, FeLV, and feline syncytium-forming virus (FeSFV), which is different from the first two viruses because it is considered non-pathogenic in nature [8].…”

“…Although acquired immunity, both cellular and humoral, plays a crucial role in the resistance to HIV infection, there is not yet a consensus as to which mechanisms are truly protective. With regard to the cellular immune response in ESN individuals, some reports indicate a strong anti-HIV response by non-cytotoxic CD8 + T cells, the recognition of a different epitope compared with seropositive individuals, and a greater Th1 response that is characterised by an increased production of IL-2 and IFN␥ and a reduced IL-10 production [56,57]. Nevertheless, a low lymphocyte activation was also shown to reduce the susceptibility to HIV infection because lymphocyte activation is needed for viral replication and is associated with the pathogenesis of the disease [7,56].…”