Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever

Shuiyun Lan, Wun Ju Shieh, Qinfeng Huang, Sherif R. Zaki, Yuying Liang, Hinh Ly

Research output: Contribution to journalArticlepeer-review

Abstract

Arenaviruses, such as Lassa virus (LASV), can cause severe and fatal hemorrhagic fevers (e.g., Lassa fever, LF) in humans with no vaccines or therapeutics. Research on arenavirus-induced hemorrhagic fevers (AHFs) has been hampered by the highly virulent nature of these viral pathogens, which require high biocontainment laboratory, and the lack of an immune-competent small animal model that can recapitulate AHF disease and pathological features. Guinea pig infected with Pichinde virus (PICV), an arenavirus that does not cause disease in humans, has been established as a convenient surrogate animal model for AHFs as it can be handled in a conventional laboratory. The PICV strain P18, derived from sequential passaging of the virus 18 times in strain 13 inbred guinea pigs, causes severe febrile illness in guinea pigs that is reminiscent of lethal LF in humans. As inbred guinea pigs are not readily available and are difficult to maintain, outbred Hartley guinea pigs have been used but they show a high degree of disease heterogeneity upon virulent P18 PICV infection. Here, we describe an improved outbred guinea-pig infection model using recombinant rP18 PICV generated by reverse genetics technique followed by plaque purification, which consistently shows >90% mortality and virulent infection. Comprehensive virological, histopathological, and immunohistochemical analyses of the rP18-virus infected animals show similar features of human LASV infection. Our data demonstrate that this improved animal model can serve as a safe, affordable, and convenient surrogate small animal model for studying human LF pathogenesis and for evaluating efficacy of preventative or therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)1131-1141
Number of pages11
JournalVirulence
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2020

Bibliographical note

Funding Information:
We thank J. Aronson (University of Texas Medical Branch) for providing the parental P2 and P18 stock viruses, K. Conzelmann (Ludwig-Maximilians-Universität, Germany) for the BSRT7-5 cells. Research reported in this publication was supported in parts by NIH grants R01 AI083409 (YL), R01 AI093580 (HL), and AI131586 (YL and HL).

Keywords

  • Arenavirus
  • Lassa virus
  • Pichinde virus
  • animal model
  • mammarenavirus
  • pathogenesis
  • pathology
  • surrogate model
  • virulence

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