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Review
. 2019 Feb 5;20(3):685.
doi: 10.3390/ijms20030685.

Role of Immunogenetics in the Outcome of HCMV Infection: Implications for Ageing

Anna Aiello  1 , Giulia Accardi  2 , Giuseppina Candore  3 , Calogero Caruso  4 , Claudia Colomba  5 , Danilo Di Bona  6 , Giovanni Duro  7 , Caterina Maria Gambino  8 , Mattia Emanuela Ligotti  9 , Janardan P Pandey  10
Affiliations
Review

Role of Immunogenetics in the Outcome of HCMV Infection: Implications for Ageing

Anna Aiello et al. Int J Mol Sci. .

Abstract

The outcome of host-virus interactions is determined by a number of factors, some related to the virus, others to the host, such as environmental factors and genetic factors. Therefore, different individuals vary in their relative susceptibility to infections. Human cytomegalovirus (HCMV) is an important pathogen from a clinical point of view, as it causes significant morbidity and mortality in immunosuppressed or immunosenescent individuals, such as the transplanted patients and the elderly, respectively. It is, therefore, important to understand the mechanisms of virus infection control. In this review, we discuss recent advances in the immunobiology of HCMV-host interactions, with particular emphasis on the immunogenetic aspects (human leukocyte antigens, HLA; killer cell immunoglobulin-like receptors, KIRs; immunoglobulin genetic markers, GM allotypes) to elucidate the mechanisms underlying the complex host-virus interaction that determine various outcomes of HCMV infection. The results, which show the role of humoral and cellular immunity in the control of infection by HCMV, would be valuable in directing efforts to reduce HCMV spurred health complications in the transplanted patients and in the elderly, including immunosenescence. In addition, concerning GM allotypes, it is intriguing that, in a Southern Italian population, alleles associated with the risk of developing HCMV symptomatic infection are negatively associated with longevity.

Keywords: GM; HCMV; HLA; KIR; NK; antibodies; elderly; immunosenescence.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The figure shows the killer cell immunoglobulin-like receptor (KIR)/ human leukocyte antigens (HLA) interaction with inhibitory or activating effects. The activating receptors (↓) have short cytoplasmic tails lacking cytoplasmic immunoreceptor tyrosine-based inhibition motif (ITIM). The tails interact with the adaptor molecule, the death associated protein (DAP) 12, and contain immunoreceptor tyrosine-based activation motif (ITAM) linked to protein tyrosine kinase activation pathways. On the contrary, the inhibitory KIRs (⟘) are characterized by the presence of ITIM, which recruits the SH protein-1/2 tyrosine phosphatases. In the figure, the receptors, inhibitory or activating, and the HLA ligands, that interact are marked with the same colour. The ligands of the receptors marked in black are unknown. The interaction between KIR3DL2 and HLA-A-Bw4 is inhibitory. The four blue spheres depict the four domains of the HLA complex. The two yellow spheres depict the two immunoglobulin-like extracellular domains of KIR. However, the figure does not show KIRs that have three immunoglobulin-like extracellular domains.
See this image and copyright information in PMC

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