Human Cytomegalovirus-Encoded microRNAs Can Be Found in Saliva Samples from Renal Transplant Recipients.

Shelley Waters,Bing H Wang,Kylie Munyard,Ashley Irish,Patricia Price,Silvia Lee

doi:10.3390/ncrna6040050

Abstract

Human cytomegalovirus (HCMV) infections are common following renal transplantation and may have long-lasting effects. HCMV can be measured directly by viral DNA or indirectly via host immune responses. HCMV-encoded microRNA (miRNA) may alter the pathobiology of HCMV infections and contribute to the progression of HCMV disease. HCMV-encoded miRNAs can be detected in blood but have not been sought in saliva. We investigated saliva samples from 32 renal transplant recipients (RTR) and 12 seropositive healthy controls for whom immunological data was available. Five HCMV-encoded miRNAs (miR-UL112-5p, miR-US5-2-3p, miR-UL36, miR-US25-2-3p and miR-UL22A) were sought using primer probe assays. HCMV miRNA species were detected in saliva from 15 RTR and 3 healthy controls, with miR-US5-2-3p most commonly detected. The presence of HCMV miRNAs associated with increased T-cell responses to HCMV IE-1 in RTR, suggesting a link with frequent reactivations of HCMV.

Highlights

Despite prophylactic measures, human cytomegalovirus (HCMV) remains a significant pathogen following renal transplantation, where infections contribute to end-organ disease, graft rejection and secondary bacterial and fungal infections [1]
Thirty-two saliva samples from renal transplant recipients (RTR) with detectable HCMV DNA or high levels of circulating antibodies were compared with 12 seropositive healthy controls
There were no significant differences in age, sex or ethnicity between healthy controls and RTR (Table 1)

Summary

Introduction

Human cytomegalovirus (HCMV) remains a significant pathogen following renal transplantation, where infections contribute to end-organ disease, graft rejection and secondary bacterial and fungal infections [1]. HCMV is routinely monitored by the presence of viral DNA. HCMV does not replicate in blood leukocytes, so its DNA is often undetectable in blood or plasma [2]. Acinar cells of the salivary gland support HCMV replication and may be a prominent site of HCMV latency. The presence of HCMV in a host has been assessed using antibody and T-cell responses, even though these are influenced by the host’s immunological capacity—notably in human immunodeficiency virus (HIV) patients [3]. Levels of IgG antibodies reactive with HCMV antigens reflect a lifetime history of infection and the cumulative viral burden. HCMV-reactive antibodies rise with age, and higher titres are associated with all-cause mortality, development of cardiovascular diseases and reduced responses to influenza vaccination in elderly populations [5]

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Results

Conclusion