Enteric viruses replicate in salivary glands and infect through saliva

S. Ghosh, M. Kumar, M. Santiana, A. Mishra, M. Zhang, H. Labayo, A. M. Chibly, H. Nakamura, T. Tanaka, W. Henderson, E. Lewis, O. Voss, Y. Su, Y. Belkaid, J. A. Chiorini, M. P. Hoffman and N. Altan-Bonnet ()
Additional contact information
S. Ghosh: National Heart Lung and Blood Institute, National Institutes of Health
M. Kumar: National Heart Lung and Blood Institute, National Institutes of Health
M. Santiana: National Heart Lung and Blood Institute, National Institutes of Health
A. Mishra: National Heart Lung and Blood Institute, National Institutes of Health
M. Zhang: National Heart Lung and Blood Institute, National Institutes of Health
H. Labayo: National Heart Lung and Blood Institute, National Institutes of Health
A. M. Chibly: National Institute of Dental and Craniofacial Research, National Institutes of Health
H. Nakamura: National Institute of Dental and Craniofacial Research, National Institutes of Health
T. Tanaka: National Institute of Dental and Craniofacial Research, National Institutes of Health
W. Henderson: University of Connecticut
E. Lewis: National Institute of Allergy and Infectious Diseases, National Institutes of Health
O. Voss: University of Maryland School of Medicine
Y. Su: National Institutes of Health
Y. Belkaid: National Institute of Allergy and Infectious Diseases, National Institutes of Health
J. A. Chiorini: National Institute of Dental and Craniofacial Research, National Institutes of Health
M. P. Hoffman: National Institute of Dental and Craniofacial Research, National Institutes of Health
N. Altan-Bonnet: National Heart Lung and Blood Institute, National Institutes of Health

Nature, 2022, vol. 607, issue 7918, 345-350

Abstract: Abstract Enteric viruses like norovirus, rotavirus and astrovirus have long been accepted as spreading in the population through fecal–oral transmission: viruses are shed into feces from one host and enter the oral cavity of another, bypassing salivary glands (SGs) and reaching the intestines to replicate, be shed in feces and repeat the transmission cycle1. Yet there are viruses (for example, rabies) that infect the SGs2,3, making the oral cavity one site of replication and saliva one conduit of transmission. Here we report that enteric viruses productively and persistently infect SGs, reaching titres comparable to those in the intestines. We demonstrate that enteric viruses get released into the saliva, identifying a second route of viral transmission. This is particularly significant for infected infants, whose saliva directly transmits enteric viruses to their mothers’ mammary glands through backflow during suckling. This sidesteps the conventional gut–mammary axis route4 and leads to a rapid surge in maternal milk secretory IgA antibodies5,6. Lastly, we show that SG-derived spheroids7 and cell lines8 can replicate and propagate enteric viruses, generating a scalable and manageable system of production. Collectively, our research uncovers a new transmission route for enteric viruses with implications for therapeutics, diagnostics and importantly sanitation measures to prevent spread through saliva.

Date: 2022
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DOI: 10.1038/s41586-022-04895-8

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