Abstract
The genetic factors associated with susceptibility or resistance to viral infections are likely to involve a sophisticated array of immune response. These genetic elements may modulate other biological factors that account for significant influence on the gene expression and/or protein function in the host. Among them, the role of the major histocompatibility complex in viral pathogenesis in particular human immunodeficiency virus (HIV) and hepatitis C virus (HCV), is very well documented. We, recently, added a novel insight into the field by identifying the molecular mechanism associated with the protective role of human leukocyte antigen (HLA)-B27/B57 CD8+ T cells in the context of HIV-1 infection and why these alleles act as a double-edged sword protecting against viral infections but predisposing the host to autoimmune diseases. The focus of this review will be reexamining the role of classical and non-classical HLA alleles, including class Ia (HLA-A, -B, -C), class Ib (HLA-E, -F, -G, -H), and class II (HLA-DR, -DQ, -DM, and -DP) in immune regulation and viral pathogenesis (e.g., HIV and HCV). To our knowledge, this is the very first review of its kind to comprehensively analyze the role of these molecules in immune regulation associated with chronic viral infections.
Highlights
Chronic viral infection imposes major selective pressure on the host’s immune system
We have shown that CTLs restricted by human leukocyte antigen (HLA)-B27 and HLA-B57 are able to evade Treg-mediated suppression during chronic infection by killing Tregs they encounter in a granzyme B (GzmB)-dependent manner [22]
Some differences in the methodology and clinical endpoints might be accountable for some discrepancies reported for some HLA alleles by different groups
Summary
Chronic viral infection imposes major selective pressure on the host’s immune system. It has been shown that susceptibility and/or disease progression in a patient with a chronic viral infection, such as hepatitis C virus (HCV) or human immunodeficiency virus (HIV), is influenced by host genetic factors [1, 2] Following their discovery in the 1970s [3], human leukocyte antigen (HLA) loci appeared to be a leading genetic candidate for infectious disease susceptibility. Extreme polymorphism and possible mutations in the MHC increases the chance of autoimmune diseases [10] These molecules play an important role in the regulation of host’s immune response as presenters of self-and/or foreign peptides/antigens to T cell receptors (TCRs) for initiating of tolerance and cytotoxic T cell (CTL) or helper T cell response [11] (Figure 2). Different groups have defined LTNPs in different ways but, in our studies, we have defined them as individuals who have been infected with HIV more than 10 years, showing low detectable plasma viremia
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