The Detection of CMV in Saliva Can Mark a Systemic Infection with CMV in Renal Transplant Recipients.

Shelley Waters,Megan Lloyd,Patricia Price,Silvia Lee,Ashley Irish

doi:10.3390/ijms20205230

Abstract

Human cytomegalovirus (CMV) is often transmitted through saliva. The salivary gland is a site of CMV replication and saliva can be used to diagnose congenital CMV infections. CMV replication is monitored in whole blood or plasma in renal transplant recipients (RTR) and associates with clinical disease. However, these assays may not detect replication in the salivary gland and there is little data linking detection in saliva with systemic infection and clinical sequelae. RTR (n = 82) were recruited > 2 years after transplantation. An in-house quantitative PCR assay was used to detect CMV UL54 in saliva samples. CMV DNA was sought in plasma using a commercial assay. Vascular health was predicted using flow mediated dilatation (FMD) and plasma biomarkers. CMV-reactive antibodies were quantified by ELISA and circulating CMV-specific T-cells by an interferon-γ ELISpot assay. Vδ2− γδ T-cells were detected using multicolor flow cytometry reflecting population expansion after CMV infection. The presence of CMV DNA in saliva and plasma associated with plasma levels of antibodies reactive with CMV gB and with populations of circulating Vδ2− γδ T -cells (p < 0.01). T-cells reactive to CMV immediate early (IE)-1 protein were generally lower in patients with CMV DNA in saliva or plasma, but the level of significance varied (p = 0.02–0.16). Additionally, CMV DNA in saliva or plasma associated weakly with impaired FMD (p = 0.06–0.09). The data suggest that CMV detected in saliva reflects systemic infections in adult RTR.

Highlights

Human cytomegalovirus (CMV) is a beta-herpesvirus carried by ~83% of the global adult population [1]
The presence of CMV DNA in saliva or plasma from renal transplant recipients (RTR) associated with plasma levels of CMV antibodies detected with gB antigen (Figure 1A, p = 0.009 and Figure 1B, p = 0.006) and populations of Vδ2− γδ T-cells (Figure 1C, p = 0.01 and Figure 1D, p = 0.005)
Presence of CMV DNA in saliva associated with increased T-cell responses to the VLE peptide (Figure 1G, p = 0.02) which is a component of the immediate early (IE)-1 antigen

Summary

Introduction

Human cytomegalovirus (CMV) is a beta-herpesvirus carried by ~83% of the global adult population [1]. High titers of CMV-reactive IgG antibodies have been associated with all-cause mortality, development of CVD and reduced responses to influenza vaccination in elderly populations [5]. High CMV antibody levels in individuals living with human immunodeficiency virus (HIV) are associated with cerebrovascular disease and CVD [6]. Once HIV patients are stable on therapy, higher T-cell responses ( CD8+ T-cell responses to immediate early (IE)-1 protein) suggest a high burden of CMV [8]. This response may represent a lifetime of persistent infections that are predominantly latent, as in older CMV seropositive adults, up to 23% of the entire CD8+ T-cell compartment can be CMV-specific [9]

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