Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Feb 14:13:826074.
doi: 10.3389/fimmu.2022.826074. eCollection 2022.

Role of HLA-G in Viral Infections

Simon Jasinski-Bergner  1 , Dominik Schmiedel  2 , Ofer Mandelboim  3 , Barbara Seliger  1   2
Affiliations
Review

Role of HLA-G in Viral Infections

Simon Jasinski-Bergner et al. Front Immunol. .

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.

Keywords: human leukocyte antigen G; immune escape; interleukin 10; viral infection; virus-induced tumors.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Summary of HLA-G isoforms with their binding positions for the so far known receptors. This schematic summary of the structural differences of HLA-G isoforms shows the so far known HLA-G receptors and also designates the exact binding position. The black arrows show exemplarily, but not exclusively possible interactions, depending on mentioned binding positions on the HLA-G ligands. There exist first evidence of a possible interaction between NKG2A with HLA-G, which still needs to be investigated in more detail. Therefore, NKG2A is not yet mentioned within this scheme. Created with BioRender.com.
Figure 2
Figure 2
Scheme summarizing the virus-induced enhanced IL-10 secretion resulting in elevated HLA-G expression and secretion. The working hypothesis demonstrates the elevated IL-10 secretion of certain immune effector cells as consequence of viral infections, which is very likely the main driver of the increased HLA-G gene expression and secretion within the virally infected host cells strongly contributing to immune evasion. Created with BioRender.com.
See this image and copyright information in PMC

References

    1. Rai KR, Shrestha P, Yang B, Chen Y, Liu S, Maarouf M, et al. . Acute Infection of Viral Pathogens and Their Innate Immune Escape. Front Microbiol (2021) 12:672026. doi: 10.3389/fmicb.2021.672026 - DOI - PMC - PubMed
    1. Monette A, Mouland AJ. T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders. Int Rev Cell Mol Biol (2019) 342:175–263. doi: 10.1016/bs.ircmb.2018.07.006 - DOI - PMC - PubMed
    1. Finlay BB, McFadden G. Anti-Immunology: Evasion of the Host Immune System by Bacterial and Viral Pathogens. Cell (2006) 124(4):767–82. doi: 10.1016/j.cell.2006.01.034 - DOI - PubMed
    1. Ishitani A, Geraghty DE. Alternative Splicing of HLA-G Transcripts Yields Proteins With Primary Structures Resembling Both Class I and Class II Antigens. Proc Natl Acad Sci USA (1992) 89(9):3947–51. doi: 10.1073/pnas.89.9.3947 - DOI - PMC - PubMed
    1. Carosella ED, Moreau P, Lemaoult J, Rouas-Freiss N. HLA-G: From Biology to Clinical Benefits. Trends Immunol (2008) 29(3):125–32. doi: 10.1016/j.it.2007.11.005 - DOI - PubMed

Publication types