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

Anna Aiello,Calogero Caruso,Janardan P Pandey,Mattia Emanuela Ligotti,Danilo Di Bona,Caterina Maria Gambino,Giovanni Duro,Claudia Colomba,Giuseppina Candore,Giulia Accardi

doi:10.3390/ijms20030685

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.

Highlights

Both environmental and genetic factors, as well as factors related to viruses, play a key role in determining the outcome of viral infections
It is well known that human cytomegalovirus (HCMV) is an important pathogen from a clinical point of view, because it causes significant morbidity and mortality in immunosuppressed individuals such as the transplanted patients and the elderly, in turn exacerbating their immunosenescence [3,4]
It is intriguing that in a study performed on Human cytomegalovirus (HCMV) infection in Ireland, human leukocyte antigens (HLA)-A1, HLA-B8 alleles were associated with HCMV seronegativity [5]

Summary

Introduction

Both environmental and genetic factors, as well as factors related to viruses, play a key role in determining the outcome of viral infections. It is well known that human cytomegalovirus (HCMV) is an important pathogen from a clinical point of view, because it causes significant morbidity and mortality in immunosuppressed individuals such as the transplanted patients and the elderly, in turn exacerbating their immunosenescence [3,4] It is, important to understand the underlying mechanisms of virus infection control. There is triggering of acquired immunity that involves both T and B lymphocytes It results in a large cytotoxic CD8 T cell response that plays a key role in the control of primary HCMV infection and reactivation from latency. Data are discussed considering the role of HCMV in ageing and immunosenescence

HLA and HCMV

KIR and HCMV

GM Allotypes and HCMV

Findings

Summary