Primary Site of Coxsackievirus B Replication in the Small Intestines: No Proof of Peyer's Patches Involvement.

Shubhada Bopegamage,Jochem Galama,Katarina Berakova,Renata Baksova,Pavol Gomocak,Heikki Hyoty,Sisko Tauriainen

doi:10.3390/microorganisms9122600

Shubhada Bopegamage, Jochem Galama + Show 5 more

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https://doi.org/10.3390/microorganisms9122600

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Journal: Microorganisms	Publication Date: Dec 16, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: Slovak Medical University, University of Turku

Abstract

Background: Enterovirus (EV) infections are associated with a broad range of diseases. Since the first experimental infection of primates with poliovirus (PV), tonsils and the Peyer’s patches (PPs) have been believed to be the primary replication sites of EVs. Our aim was to localize different viral markers in the small intestines (SI) of coxsackievirus B (CVB) orally and intraperitoneally (i.p.) infected mice. Methods: Transverse sections of SIs of both infected and control male outbred mice were collected at different intervals post-infection (p.i) and analyzed for presence of interferon-alpha (IFN-α) and viral protein VP1 by immunohistochemistry and in situ hybridization (ISH). Fluorescent marker, eGFP, was identified in cryosections of mice infected with eGFP-CVB3. Results: In the infected SIs, we observed enlarged germinating centers (GCs) in the PPs; IFN-α was detected in the PPs and mucosal layer of the SIs. However, VP1, viral RNA and the eGFP were absent in the GCs of PPs at all stages of infection irrespective of the virus strains used. Conclusions: Virus was present in the epithelial cells but not in GCs of the PPs of the murine SIs. Our results do not support the hypothesis of EV replication in the PP especially in the GCs.

Highlights

Genus Enterovirus belongs to the family Picornaviridae, it is classified into fifteen species of which seven (Enterovirus-A, -B, -C and -D, and Rhinovirus-A, -B and -C) are human pathogens
The Peyer’s patches (PPs)’s showed activated germinating centers (GCs) after coxsackievirus B (CVB) infections (Figure 1a), the number of activated or enlarged PPs were increased after oral infection as compared to the control (Figure 1b)
We have localized the viral markers in the small intestines (SI) and followed up the PPs

Summary

Introduction

Genus Enterovirus belongs to the family Picornaviridae, it is classified into fifteen species of which seven (Enterovirus-A, -B, -C and -D, and Rhinovirus-A, -B and -C) are human pathogens. These viruses are transmitted by the fecal-oral and respiratory routes. Enteroviruses (EVs) are common around the world and cause a variety of diseases in humans, ranging from mild and asymptomatic to severe life threatening central nervous system (CNS) and systemic infections. Since the first experimental infection of primates with poliovirus (PV), tonsils and the Peyer’s patches (PPs) have been believed to be the primary replication sites of EVs. Our aim was to localize different viral markers in the small intestines (SI) of coxsackievirus B (CVB) orally and intraperitoneally (i.p.).

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