Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid

Walker, Forrest C.; Hassan, Ebrahim; Peterson, Stefan T.; Rodgers, Rachel; Schriefer, Lawrence A.; Thompson, Cassandra E; Li, Yuhao; Kalugotla, Gowri; Blum-Johnston, Carla; Lawrence, Dylan; McCune, Broc T.; Graziano, Vincent R.; Lushniak, Larissa; Lee, Sang‐Hyun; Roth, Alexa N.; Karst, Stephanie M.; Nice, Timothy J.; Miner, Jonathan J.; Wilen, Craig B.; Baldridge, Megan T.

doi:10.1371/journal.ppat.1009402

Cited by 12 publications

(12 citation statements)

References 83 publications

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“…1b,c and Extended Data Fig. 1a,b ), MNV-3, MNV-4 and the less-well-characterized WU23 murine norovirus strains persistently infect the proximal colon and shed into feces for weeks 22 – 25 . We inoculated mice with these strains and found that all were also persistently shed in saliva for at least 3 weeks after inoculation, with titres approximately 10 3 -fold higher than input (6 hpi) (Fig.…”

Section: Enteric Viruses Are Transmitted Through Salivamentioning

confidence: 97%

Enteric viruses replicate in salivary glands and infect through saliva

Ghosh

Kumar

Santiana

et al. 2022

Nature

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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 cycle 1 . Yet there are viruses (for example, rabies) that infect the SGs 2 , 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 route 4 and leads to a rapid surge in maternal milk secretory IgA antibodies 5 , 6 . Lastly, we show that SG-derived spheroids 7 and cell lines 8 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.

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Section: Enteric Viruses Are Transmitted Through Salivamentioning

confidence: 97%

Enteric viruses replicate in salivary glands and infect through saliva

Ghosh

Kumar

Santiana

et al. 2022

Nature

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“…Transmission electron microscopy images of MGDG-treated HSV-2 particles showed that MGDG treatment might cause morphological changes in not only the envelope but also the capsids of the virus particles, as judged from the reduction of their diameter. The MNV capsid plays a crucial role in binding to its receptor on host cells [16].…”

Section: Discussionmentioning

confidence: 99%

“…In this study, it was obtained from Dr. Tohya, Nihon University, Japan. This strain has been widely used in investigating the receptor for MNV [35] and tests for virucidal and antiviral substances [16,36]. The MNV S7-PP3 strain was propagated in RAW 264.7 cells (ATCC TIB-71).…”

Section: Cells and Virusesmentioning

confidence: 99%

Virucidal and Immunostimulating Activities of Monogalactosyl Diacylglyceride from Coccomyxa sp. KJ, a Green Microalga, against Murine Norovirus and Feline Calicivirus

et al. 2022

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Human noroviruses are the most common pathogens causing acute gastroenteritis and may lead to more severe illnesses among immunosuppressed people, including elderly and organ transplant recipients. To date, there are no safe and effective vaccines or antiviral agents for norovirus infections. In the present study, we aimed to demonstrate the antiviral activity of monogalactosyl diacylglyceride (MGDG) isolated from a microalga, Coccomyxa sp. KJ, against murine norovirus (MNV) and feline calicivirus (FCV), the surrogates for human norovirus. MGDG showed virucidal activities against these viruses in a dose- and time-dependent manner—MGDG at 100 μg/mL reduced the infectivity of MNV and FCV to approximately 10% after 60 min incubation. In the animal experiments of MNV infection, intraoral administration of MGDG (1 mg/day) exerted a therapeutic effect by suppressing viral shedding in the feces and produced high neutralizing antibody titers in sera and feces. When MGDG was orally administered to immunocompromised mice treated with 5-fluorouracil, the compound exhibited earlier stopping of viral shedding and higher neutralizing antibody titers of sera than those in the control mice administered with distilled water. Thus, MGDG may offer a new therapeutic and prophylactic alternative against norovirus infections.

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“…There are data to support a cellular tropism for intestinal epithelial [43][44][45] and/or immune cells [46][47][48][49] for HNoV and MNoV that may be strain-specific. Recent insights, which will be subsequently defined, have demonstrated crucial aspects of MNoV-IFN interactions in regulating virulence as well as cellular tropism of this prominent pathogen [50][51][52].…”

Section: Trends In Immunologymentioning

confidence: 99%