Differential Pathogenesis Between Andes Virus Strains Chi-7913 And Chile-9717869 In Syrian Hamsters

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-791 3 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.