Hearing loss in outbred Hartley guinea pigs experimentally infected with Pichinde virus as a surrogate model of human mammarenaviral hemorrhagic fevers

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Lassa fever (LF) is a neglected tropical disease that is caused by Lassa virus (LASV), a human hemorrhagic fever-causing mammarenavirus. A notable sequela of LF is sensorineural hearing loss (SNHL) that can develop in about 33% of the patients. Animal models of LF-associated SNHL have been limited in size and scope because LASV is a biosafety level 4 (BSL4) pathogen that requires its handling in a high biocontainment laboratory. In this report, we describe the development of an alternative arenavirus hearing loss model by infecting outbred Hartley guinea pigs with a virulent strain (rP18) of the Pichinde virus (PICV), which is a guinea pig-adapted mammarenavirus that has been used as a surrogate model of mammarenaviral hemorrhagic fevers in a conventional (BSL2) laboratory. By measuring auditory brainstem response (ABR) throughout the course of the virulent rP18 PICV infection, we noticed that some of the animals experienced an acute but transient level of hearing loss. Cochleae of hearing-impaired animals, but not of controls, had demonstrable viral RNA by quantitative RT-PCR, indicating the presence of virus in the affected inner ear with no overt histopathological changes. In contrast, neither the outbred Hartley guinea pigs infected with a known avirulent strain (rP2) of PICV nor those that were mock-infected showed any evidence of hearing loss or viral infection of the inner ear. This is the first report of an immunocompetent small animal model of mammarenavirus-induced hearing loss that can be used to evaluate potential therapeutics against virus-induced hearing impairment under a conventional laboratory setting.

Original languageEnglish (US)
Pages (from-to)1049-1061
Number of pages13
Issue number1
StatePublished - 2022

Bibliographical note

Funding Information:
The authors would like to thank Dr. A. Rendahl at the University of Minnesota for his assistance with statistical analysis. This work was supported in part by the NIH NIAID grant R01 AI131586 to HL and YL, by a predoctoral NIH fellowship T32 DA007097 and the University of Minnesota Doctoral Dissertation Fellowship (DDF) to MB, and by a predoctoral NIH fellowship T32 OD010993 to NK.

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.


  • Arenavirus
  • Lassa virus
  • Mammarenavirus
  • Pichinde virus
  • Sensorineural hearing loss (SNHL)
  • Virus-induced hearing loss
  • guinea pigs

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural


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