Differential Pathogenesis between Andes Virus Strains CHI-7913 and Chile-9717869 in Syrian Hamsters
- 26 April 2021
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 95 (10)
- https://doi.org/10.1128/jvi.00108-21
Abstract
Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory disease caused by orthohantaviruses in the Americas with a fatality rate as high as 35%. In South America, Andes orthohantavirus (Hantaviridae, Orthohantavirus; ANDV) is a major cause of HCPS, particularly in Chile and Argentina, where thousands of cases have been reported since the virus was discovered. Two strains of ANDV that are classically used for experimental studies of the virus are Chile-9717869, isolated from the natural reservoir, the long-tailed pygmy rice rat, and CHI-7913, an isolate from a lethal human case of HCPS. An important animal model for studying pathogenesis of HCPS is the lethal Syrian golden hamster model of ANDV infection. In this model, ANDV strain Chile-9717869 is uniformly lethal and has been used extensively for pathogenesis, vaccination, and therapeutic studies. Here, we show that the CHI-7913 strain, despite having high sequence similarity with Chile-9717869, does not cause lethal disease in Syrian hamsters. CHI-7913, while being able to infect hamsters and replicate to moderate levels, showed a reduced ability to replicate within the tissues compared with Chile-9717869. Hamsters infected with CHI-7913 had reduced expression of cytokines interleukin-4 (IL-4), IL-6, and gamma interferon compared with Chile-9717869-infected animals, suggesting potentially limited immune-mediated pathology. These results demonstrate that certain ANDV strains may not be lethal in the classical Syrian hamster model of infection, and further exploration into the differences between lethal and nonlethal strains should provide important insights into molecular determinants of pathogenic hantavirus infection. IMPORTANCE Andes orthohantavirus (ANDV) is a New World hantavirus that is a major cause of hantavirus cardiopulmonary syndrome (HCPS; also referred to as hantavirus pulmonary syndrome) in South America, particularly in Chile and Argentina. ANDV is one of the few hantaviruses for which there is a reliable animal model, the Syrian hamster model, which recapitulates important aspects of human disease. Here, we infected hamsters with a human isolate of ANDV, CHI-7913, to assess its pathogenicity compared with the classical lethal Chile-9717869 strain. CHI-7913 had 22 amino acid differences from Chile-9717869, did not cause lethal disease in hamsters, and showed reduced ability to replicate in vivo. Our data indicate potentially important molecular signatures for the pathogenesis of ANDV infection in hamsters and may lead to insights into what drives the pathogenesis of certain hantaviruses in humans.Funding Information
- Public Health Agency of Canada (Internal funding)
This publication has 52 references indexed in Scilit:
- Diversity and Distribution of Hantaviruses in South AmericaJournal of Virology, 2012
- Vesicular Stomatitis Virus-Based Vaccine Protects Hamsters against Lethal Challenge with Andes VirusJournal of Virology, 2011
- T Cells Are Not Required for Pathogenesis in the Syrian Hamster Model of Hantavirus Pulmonary SyndromeJournal of Virology, 2011
- In Vitro and In Vivo Activity of Ribavirin against Andes Virus InfectionPLOS ONE, 2011
- A Global Perspective on Hantavirus Ecology, Epidemiology, and DiseaseClinical Microbiology Reviews, 2010
- Adenovirus Vectors Expressing Hantavirus Proteins Protect Hamsters against Lethal Challenge with Andes VirusJournal of Virology, 2009
- Role of mixed Th1 and Th2 serum cytokines on pathogenesis and prognosis of hantavirus pulmonary syndromeMicrobes and Infection, 2008
- Immune Serum Produced by DNA Vaccination Protects Hamsters against Lethal Respiratory Challenge with Andes VirusJournal of Virology, 2008
- Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virusProceedings of the National Academy of Sciences of the United States of America, 2007
- Regulatory T cells enhance persistence of the zoonotic pathogen Seoul virus in its reservoir hostProceedings of the National Academy of Sciences of the United States of America, 2007