Natural history of postnatal rhesus cytomegalovirus shedding by dams and acquisition by infant rhesus monkeys.

Amitinder Kaur,Hannah L Itell,E Peek Ehlinger,Sallie R Permar,Valerie Varner,Soren Gantt,Juliet V Spencer

doi:10.1371/journal.pone.0206330

Abstract

BackgroundHuman infants frequently acquire human cytomegalovirus (HCMV) through breastfeeding, resulting in persistent high-level viral shedding in saliva and urine and infectivity to others, including pregnant women. Thus, vaccination to interrupt postnatal HCMV transmission is an attractive strategy to prevent HCMV spread and congenital infection. Rhesus CMV (RhCMV) in nonhuman primates is a valuable model for the study of immune strategies to prevent CMV transmission. Although rhesus monkeys typically acquire RhCMV before 1 year of age, the timing and mode of natural infant RhCMV transmission remain unknown.MethodsWe followed 5 RhCMV-seropositive dams and their infants from birth until weaning, approximately 6 months later. RhCMV DNA levels in plasma, breast milk, saliva, and urine were measured every 2 weeks by quantitative PCR. RhCMV-specific T cell responses in peripheral blood and breast milk were measured by interferon gamma ELISpot assays. Serum IgG antibody levels were measured by ELISA.ResultsFour of five postpartum RhCMV-seropositive mothers had intermittent, low-level RhCMV shedding in breast milk, whereas all had high-magnitude RhCMV shedding in saliva and urine. The kinetics of maternal blood RhCMV-specific T cell responses and viral shedding in urine and saliva did not strongly associate, though dams with consistently high systemic RhCMV-specific T cell responses tended to have undetectable RhCMV shedding in breast milk. All RhCMV-exposed infants had intermittent, low-level RhCMV shedding in saliva during the lactation period, with minimal systemic RhCMV-specific T cell responses.ConclusionsDespite exposure to RhCMV shedding in breast milk and other maternal fluids, postnatal mother-to-child RhCMV transmission appears to be less efficient than that of HCMV. A greater understanding of the determinants of RhCMV transmission and its usefulness as a model of HCMV mucosal acquisition may provide insight into strategies to prevent HCMV infections in humans.

Highlights

Human cytomegalovirus (HCMV) is a ubiquitous human virus, infecting more than half of the U.S population [1] and >90% of populations in developing regions [2]
The kinetics of maternal blood Rhesus CMV (RhCMV)-specific T cell responses and viral shedding in urine and saliva did not strongly associate, though dams with consistently high systemic RhCMV-specific T cell responses tended to have undetectable RhCMV shedding in breast milk
Postnatal rhesus cytomegalovirus shedding by dams and acquisition by infant rhesus monkeys and kinetics of postpartum RhCMV shedding and the typical mode of infant RhCMV acquisition is central to establishing a model of postnatal RhCMV transmission in rhesus monkeys

Summary

Introduction

Human cytomegalovirus (HCMV) is a ubiquitous human virus, infecting more than half of the U.S population [1] and >90% of populations in developing regions [2]. HCMV is primarily transmitted through mucosal fluids, including saliva, genital fluids, and breast milk. It is the most common congenital infection worldwide and a leading cause of mortality in individuals undergoing transplantation. A vaccine interrupting postnatal HCMV transmission to infants could be a practical strategy for limiting viral spread to pregnant women with enormous potential to reduce congenital infection and disease [14]. Human infants frequently acquire human cytomegalovirus (HCMV) through breastfeeding, resulting in persistent high-level viral shedding in saliva and urine and infectivity to others, including pregnant women. Rhesus monkeys typically acquire RhCMV before 1 year of age, the timing and mode of natural infant RhCMV transmission remain unknown

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