Abstract

Clinical reports of Zika Virus (ZIKV) RNA detection in breast milk have been described, but evidence conflicts as to whether this RNA represents infectious virus. We infected post-parturient AG129 murine dams deficient in type I and II interferon receptors with ZIKV. ZIKV RNA was detected in pup stomach milk clots (SMC) as early as 1 day post maternal infection (dpi) and persisted as late as 7 dpi. In mammary tissues, ZIKV replication was demonstrated by immunohistochemistry in multiple cell types including cells morphologically consistent with myoepithelial cells. No mastitis was seen histopathologically. In the SMC and tissues of the nursing pups, no infectious virus was detected via focus forming assay. However, serial passages of fresh milk supernatant yielded infectious virus, and immunohistochemistry showed ZIKV replication protein associated with degraded cells in SMC. These results suggest that breast milk may contain infectious ZIKV. However, breast milk transmission (BMT) does not occur in this mouse strain that is highly sensitive to ZIKV infection. These results suggest a low risk for breast milk transmission of ZIKV, and provide a platform for investigating ZIKV entry into milk and mechanisms which may prevent or permit BMT.

Highlights

  • Zika virus (ZIKV) is an enveloped virus with a positive-sense, single-stranded RNA genome [1]

  • Can Zika virus be transmitted from nursing mothers to their children via breast milk? Only 4 years have passed since the Zika virus outbreak in Brazil, and much remains to be understood about the transmission and health consequences of Zika infection

  • To begin evaluating whether ZIKV could infect the mammary gland and be transmitted to breastfed infants, 8-week-old female AG129 mice were infected with ZIKV strain FSS13025

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Summary

Introduction

Zika virus (ZIKV) is an enveloped virus with a positive-sense, single-stranded RNA genome [1]. No epidemiologic data regarding ZIKV in lactating women are currently available, ZIKV RNA has been reported in breast milk from 3 [5, 9] to 33 [6] days after maternal onset of fever. Cytopathic effect (CPE) could not be demonstrated in cells cultured with either of the breast milk samples from two mothers who nursed infected infants [9]. CPE was seen upon culturing of cells with breast milk of mothers with uninfected nursing children [8, 10]. CPE was demonstrated in cells cultured with milk from a ZIKV-infected mother, and the nursing child was infected with an isolate with ZIKV genome identity of more than 99% between the infected mother and child [5]

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