[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
Detection of Zika virus in mouse mammary gland and breast milk
Jose Angel Regla-Nava, Karla M. Viramontes, Teodora Vozdolska, Anh-Thy Huynh, Tom Villani, Graeme Gardner, Michael Johnson, Pamela J. Ferro, Sujan Shresta , Kenneth Kim
Published: February 11, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007080 / This is an uncorrected proof.
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.
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 date some case reports have detected Zika virus RNA in the breast milk of infected mothers, but the presence of a virus’ RNA does not mean that intact virus is present. Milk also contains many natural defense components against infection, so even intact virus carried in breast milk may not be infectious to a child. Here we used a mouse that is genetically engineered to be highly susceptible to Zika infection, and tested whether 1) we could find intact virus in mouse breast milk and 2) infection was passed from mother to pups. We found very low levels of intact Zika virus in mouse breast milk, and found none of the nursing pups to be infected. The model of Zika virus breast milk infection developed in this study establishes a system by which we may learn whether Zika RNA in human breast milk is truly infectious to children, and how Zika virus may enter the milk.
Citation: Regla-Nava JA, Viramontes KM, Vozdolska T, Huynh A-T, Villani T, Gardner G, et al. (2019) Detection of Zika virus in mouse mammary gland and breast milk. PLoS Negl Trop Dis 13(2): e0007080. https://doi.org/10.1371/journal.pntd.0007080
Editor: David W.C. Beasley, University of Texas Medical Branch, UNITED STATES
Received: June 5, 2018; Accepted: December 14, 2018; Published: February 11, 2019
Copyright: © 2019 Regla-Nava et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was funded by NIH grants (R01 AI116813 and R21 NS100477 to S.S.) and the Chiba-UCSD Center for Mucosal Immunology, Allergy and Vaccine Development. And the La Jolla Institute for Allergy and Immunology institutional support.
Competing interests: M.J. is CEO of Visikol.
Keywords: Zika Virus; Pregnancy; Animal models.