“Stomach Viruses” hide in Salivary Glands and transmit through Saliva

Work done in the lab of Dr. Nihal Altan-Bonnet at National Institutes of Health, Bethesda, USA

About author

Sourish Ghosh completed his Bachelor of Technology in Biotechnology and joined National Brain Research Centre as a PhD student in 2010. He pursued his research in understanding the host-pathogen interactions in neurotropic viruses under the mentorship of Dr. Anirban Basu. His continued love for virology made him leave Neuroscience to work with viruses interfacing with cellular trafficking under guidance of Dr. Nihal Altan-Bonnet at National Institutes of Health, Bethesda, USA (2016-2022). Currently he is a Senior Scientist at CSIR-Indian Institute of Chemical Biology (IICB), Kolkata heading the SG’s Viral Trafficking Lab. His research interest broadly lies in understanding various viral egress mechanisms and transmission routes and developing targeted therapies.

Interview

How would you explain your research outcomes to the non-scientific community?

“Stomach Viruses” or enteric viruses like Rotavirus, Norovirus and Astroviruses are classically known to replicate in our intestines and cause diarrhea and spread through fecal-oral route of transmission. Meaning, viruses released through patient stool due to mal-sanitization practices end up mixing into our drinking water and food and further infecting our intestines. My recent discovery published in Nature, June, 2022 shows that in mouse models these viruses can replicate in salivary glands and can transmit through saliva- a much faster route of virus spread compared to the fecal-oral route. Another curious observation that I made, mouse pups (babies) infected with enteric viruses transferring viruses through saliva to their mother’s mammary glands while suckling. In response mothers release protective antibodies in milk to neutralize viruses in the pup’s intestines.

The seminal discovery emphasizes the importance of salivary glands as it acts as a reservoir for viruses as the tissue has a regulated immune response and viruses can replicate without less resistance. In addition to these, I discovered salivary gland cell lines and “mini” tissue culture models known as organoids that can propagate these enteric viruses. These easy-to-culture models will be of importance for vaccine development as apart from Rotavirus, the others do not have good vaccines. Yet, viruses like Norovirus and Astroviruses cause seasonal outbreaks infecting more than 1 billion people per year globally.

How do these findings contribute to your research area?

This discovery has opened several avenues in enteric virus research when people working in the field have almost started to think that the field has been saturated. There was a pressing need for developing vaccines against Noroviruses termed as stomach flu, notoriously known to cause outbreaks in winter months across the globe especially in the USA and Europe. The efforts were stalled due to unavailability of an easy to handle propagation cell culture system. My research shows that these viruses can grow in immortalized salivary gland cell lines.

“My research shows that these viruses can grow in immortalized salivary gland cell lines. “

What was the exciting moment during your research?

I observed a correlative increase in protective antibodies: Immunoglobulin A (IgA) in both infant’s intestines infected with the virus and milk collected from their suckling mothers who were not infected directly with the virus. There was a telling indication that the mother through a natural mechanism got alerted by the infant’s infection and released these antibodies. In hunting for the route of transmission and place of replication, I ended up discovering the virus replicating in salivary glands and transmission through saliva. This big breakthrough was achieved due to a series of careful observations and persistence resulting in two hallmarks of scientific discoveries.

What do you hope to do next?

Enteric viruses replicating in salivary glands and transmitting through saliva opens a “pandora’s box” for researchers in the field and people concerned in the public healthcare system. Being a virologist I will be interested to know why the salivary glands are prominent locations for these enteric viruses to replicate? How does our body’s immune system respond to these viruses replicating in salivary glands and whether these salivary glands act as reservoirs for these viruses? The fascinating discovery of child to mother natural feedback system and vice versa underlines the importance of breastfeeding and immune system development in infants. Understanding the basic mechanism underlying this phenomenon is another interesting direction of my research focus.

Where do you seek scientific inspiration from?

My scientific inspiration comes from discoveries that I make. Persistent efforts to reveal the underlying mechanism always drives me to uncover newer findings that have resulted in seminal studies in the field of virus research.

How do you intend to help Indian science improve?

I came back from the US terminating my H1 visa to join as a Senior Scientist, an independent research position at CSIR-Indian Institute of Chemical Biology (IICB), Kolkata. My goal is to study the interesting enteric virus phenomena from clinical patient samples in collaboration with local hospitals, hence directly participating in public healthcare research in India. In addition to these I will be training budding scientists and inspire my PhD fellows to take up science as a career and enjoy the beauty of scientific explorations.

Reference

Ghosh S, Kumar M, Santiana M, Zhang M, Mishra A, Chibly AM, Nakamura H, Tanaka T, Chiorini JA, Hoffman P., Altan-Bonnet N. Enteric viruses replicate in salivary glands and infect through saliva. Nature (2022). https://doi.org/10.1038/s41586-022-04895-8

Copy Editor

Pratibha Siwach

Regulatory Affair Specialist

Nivedita is a Postgraduate in Biotechnology, with one year Project Assistantship experience at inStem, DBT. She is currently a UPSC aspirant planning to appear for 2021 CSE. Although switching from science career to focus on governance policy and administration, her love for science remains ever-etched in all that she does. On her journey from a researcher toward public administrator, she believes in the critical role of science communication and journalism in bridging the gap between lab benches and public fields. Being part of BioPatrika is her being one stone laid for that very bridge.

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