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Characterization of inner capsid σA protein as a virulence factor of the pteropine orthoreovirus.

Hayato Harima1 Michihito Sasaki2,3 Takuma Ariizumi2 Nijiho Kawaguchi2 Hiroko Kobayashi2 Kittiya Intaruck2,4 Takeshi Kobayashi5 Takahiro Kawagishi5 Yuta Kanai5 Naganori Nao4,6 Yongjin Qiu7 Masahiro Kajihara4,6 Yasuko Orba2,3 Naoto Ito8,9 Kanako Ishihara1 Masayuki Saijo10 William W Hall3,11,12 Bernard M Hang'ombe13,14 Hirofumi Sawa3,6,12
Affiliations 14 institutions
  1. Laboratory of Veterinary Public Health, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.
  2. Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Hokkaido, Japan.
  3. Institute for Vaccine Research and Development, Hokkaido University, Hokkaido, Japan.
  4. Division of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Hokkaido, Japan.
  5. Department of Virology, Research Institute for Microbial Diseases, The University of Osaka, Osaka, Japan.
  6. One Health Research Center, Hokkaido University, Hokkaido, Japan.
  7. Laboratory of Parasitology, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.
  8. Joint Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan.
  9. Center for One Medicine Innovative Translational Research (COMIT), Institute for Advanced Study, Gifu University, Gifu, Japan.
  10. General for Health & Welfare Bureau, Public Health Office, Sapporo, Hokkaido, Japan.
  11. National Virus Reference Laboratory, School of Medicine, University College Dublin, Dublin, Ireland.
  12. Global Virus Network, Tampa, Florida, United States of America.
  13. Department of Para-clinical Studies, School of Veterinary and Medicine, the University of Zambia, Lusaka, Zambia.
  14. Copperbelt University, Kitwe, Zambia.
PMID 42189872 2026 PLoS Pathog eng epublish
PubMed DOI Browse context

Article

Publication summary

Pteropine orthoreovirus (PRV) is an emerging zoonotic virus that causes pneumonia in humans. We previously isolated the PRV strain Nachunsulwe-57 (N57) from a Zambian fruit bat and demonstrated its low virulence in laboratory mice. Here, we have attempted to identify factors responsible for differences in the virulence between strain N57 and the human-derived clinical strain Miyazaki-Bali/2007 (MB). Characterization of the virulence of recombinant monoreassortant PRVs derived from highly virulent MB and low virulent N57 strains in mice revealed that compared with wild-type (WT) MB, MB-based monoreassortants carrying the L1, S1, or S2 segment from N57 exhibited attenuated virulence. Among these, the monoreassortants carrying the S1 or S2 segment exhibited reduced viral loads and reduced cytokine gene expression levels in the lungs. Genetic mapping of virulence determinants using the reciprocal monoreassortant viruses with increased virulence demonstrated that N57-based monoreassortants carrying the S1 or S2 segment of MB exhibited enhanced virulence, resulting in lower survival rate compared with WT N57. Unlike the S1 segment, the functions of the S2 segment in pathogenesis are unclear. Thus, we further investigated the functional region of the inner-capsid σA protein encoded by the S2 segment. Notably, Ser-46 of σA was identified as a key amino acid determinant of PRV virulence and is present in strains derived from humans, monkeys, and bat flies, but not those identified from bats (their natural host). Collectively, these findings demonstrate that PRV σA is one factor that regulates virulence, and that σA Ser-46 may be related to potential interspecies transmission events from bats.

Capsid Proteins Orthoreovirus Reoviridae Infections Virulence Factors Animals Chiroptera Female Humans Mice Virulence sigma 1 protein, reovirus

Structured evidence records

Evidence records

2 total
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.88
Key finding

Ser-46 in the PRV σA protein is a key virulence determinant found in strains from humans, monkeys, and bat flies but not in bat strains, suggesting molecular adaptation linked to interspecies transmission.

Location
Not specified
Supporting text

Notably, Ser-46 of σA was identified as a key amino acid determinant of PRV virulence and is present in strains derived from humans, monkeys, and bat flies, but not those identified from bats (their natural host).

Method
genetic mapping | virulence testing in mice
Sample type
recombinant monoreassortant viruses
Study design
reverse genetics
Transmission direction
molecular mechanism only
Event type
virulence determinant associated with host origin
Genes or proteins
σA protein
Mutations
Ser-46
Mechanism types
virulence regulation | host-related adaptation
Spillover Event 1 records
Spillover Event Extraction confidence 0.90
Key finding

Pteropine orthoreovirus was isolated from a Zambian fruit bat, and human infections cause pneumonia, indicating zoonotic spillover.

Location
Zambia
Supporting text

Pteropine orthoreovirus (PRV) is an emerging zoonotic virus that causes pneumonia in humans. We previously isolated the PRV strain Nachunsulwe-57 (N57) from a Zambian fruit bat.

Method
virus isolation | strain characterization
Sample type
virus isolate
Study design
genomic surveillance
Transmission direction
animal-to-human
Event type
bat-origin human infection
Geographic raw
Zambia
Country inferred
ZMB
Genes or proteins
S1 segment | S2 segment | σA protein
Mutations
Ser-46
Mechanism types
molecular adaptation