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Review
. 2022 Jan;36(1):100669.
doi: 10.1016/j.trre.2021.100669. Epub 2021 Oct 16.

Human genetic polymorphisms and risk of viral infection after solid organ transplantation

Natalia Redondo  1 , David Navarro  2 , José María Aguado  3 , Mario Fernández-Ruiz  3
Affiliations
Review

Human genetic polymorphisms and risk of viral infection after solid organ transplantation

Natalia Redondo et al. Transplant Rev (Orlando). 2022 Jan.

Abstract

The immune system plays a key role in the host defense against viral pathogens. A signaling cascade is activated upon infection involving a variety of molecules such as pattern-recognition receptors (PRRs), interleukins or antiviral interferons. Long-term immunosuppression after solid organ transplantation (SOT) mainly abrogates adaptive T-cell-mediated responses, thus highlighting the relative contribution of innate immunity. Single-nucleotide polymorphisms (SNPs) within genes coding for PRRs or soluble mediators have been associated with differential susceptibility to viral infections among SOT recipients. A protective effect against cytomegalovirus (CMV) infection or disease has been attributed to certain SNPs in TLR9 or IFNL3 genes, whereas the opposite effect has been attributed to genetic polymorphisms in TLR2, MBL2, DC-SIGN, IL10 or IFNG. The presence of SNPs in other molecules not directly involved in innate or adaptive immune responses such as aquaporins or pregnane X appear to modulate the risk of CMV or BK polyomavirus infection, respectively. Little information is available on the genetic determinants of the post-transplant susceptibility to herpesviruses causing clinical infection (herpes simplex virus or varicella zoster virus) or the replication kinetics of components of the human blood virome used as immune surrogates (Torque teno virus). The present review critically summarizes the current knowledge on how SNP genotyping would be useful to stratify SOT recipients according to the individual risk of viral infection and proposes next research steps. Genetic susceptibility testing may improve personalized medicine and contribute to minimize the risk of viral infection after SOT.

Keywords: Cytomegalovirus; Genetic polymorphisms; Innate and adaptive immunity; SNP; Solid organ transplantation; Toll-like receptors; Torque Teno virus; Viral infections.

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