Role of HLA-G in Viral Infections

Abstract

The human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule, which has distinct features to classical HLA-A, -B, -C antigens, such as a low polymorphism, different splice variants, highly restricted, tightly regulated expression and immune modulatory properties. HLA-G expression in tumor cells and virus-infected cells, as well as the release of soluble HLA-G leads to escape from host immune surveillance. Increased knowledge of the link between HLA-G expression, viral infection and disease progression is urgently required, which highlights the possible use of HLA-G as novel diagnostic and prognostic biomarker for viral infections, but also as therapeutic target. Therefore, this review aims to summarize the expression, regulation, function and impact of HLA-G in the context of different viral infections including virus-associated cancers. The characterization of HLA-G-driven immune escape mechanisms involved in the interactions between host cells and viruses might result in the design of novel immunotherapeutic strategies targeting HLA-G and/or its interaction with its receptors on immune effector cells.

HLA-G 14-bp insertion/deletion polymorphism and risk of coronavirus disease 2019 (COVID-19) among Iraqi patients

“…There is accumulating evidence that immunosuppressive mechanisms play a major role in promoting viral infection either by suppressing the ability of infected host cells to overcome viral infection or by preventing the elimination of virus-infected cells by immune cells. One common mechanism proposed for viruses to escape immune surveillance is the loss or down-regulation of classical HLA class Ia antigens and neoexpression of non-classical HLA class Ib antigens, such as HLA-E, -F and -G [21] . In COVID-19, it has been suggested that HLA-G may be considered as potent molecules that may suppress immune functions during SARS-CoV-2 infection and thus may enhance virus subversion and allow high rates of replication [22] .…”

Evaluation of serum soluble HLA-G levels post-recovery from COVID-19 and post-vaccination (Sinopharm and Pfizer-BioNTech)

“…Although these observations were based on only one patient, they suggest evidence of an association between persistence of SARS-CoV-2, virus-induced inflammation and HLA-G expression. HLA-G induction in host cells infected with SARS-CoV-2 may represent a molecular mechanism for the development of immune evasion as proposed in several human pathogenic viruses [10] . During infection with SARS-CoV-2, the observed decrease in immune-competent cells and the up-regulated expression of pro-inflammatory cytokines is a prominent feature of immunopathology, especially in patients with severe COVID-19 [19] .…”

“…HLA-G molecules are expressed in two forms, membrane-bound antigens (HLA-G1, -G2, -G3, and -G4) and soluble proteins (sHLA-G5, -G6 and -G7). Functionally, they are potent immunomodulators and dysregulated expression of HLA-G molecules has been implicated in many pathological conditions including viral infections [10] . In COVID-19, HLA-G molecules are suggested to have immune-regulating effects and up-regulated expression of sHLA-G has been shown in patients with severe disease [11] .…”

Gestational Viral Infections: Role of Host Immune System

“…Several studies have investigated the special immunological condition reported during physiological pregnancy, evidencing the importance of specific immune-regulatory processes, in which a crucial role belongs to the major histocompatibility complex molecules, in humans HLAs (Human Leukocyte Antigens), which are also involved in the response against viral infections [ 47 , 48 ]. The loss or down-regulation of classical HLA class-Ia antigens, as well as the neo-expression of non-classical HLA class-Ib antigens (HLA-E, -F, and -G), is a frequent strategy used by viruses for evading immune surveillance [ 49 , 50 , 51 ].…”