Pathogenesis of XJ and Romero Strains of Junin Virus in Two Strains of Guinea Pigs

Abstract

Argentine hemorrhagic fever (AHF), a systemic infectious disease caused by infection with Junin virus, affects several organs, and patients can show hematologic, cardiovascular, renal, or neurologic symptoms. We compared the virulence of two Junin virus strains in inbred and outbred guinea pigs with the aim of characterizing this animal model better for future vaccine/antiviral efficacy studies. Our data indicate that this passage of the XJ strain is attenuated in guinea pigs. In contrast, the Romero strain is highly virulent in Strain 13 as well as in Hartley guinea pigs, resulting in systemic infection, thrombocytopenia, elevated aspartate aminotransferase levels, and ultimately, uniformly lethal disease. We detected viral antigen in formalin-fixed, paraffin-embedded tissues. Thus, both guinea pig strains are useful animal models for lethal Junin virus (Romero strain) infection and potentially can be used for preclinical trials in vaccine or antiviral drug development.

Differential effect of acute and persistent Junín virus infections on the nucleo-cytoplasmic trafficking and expression of heterogeneous nuclear ribonucleoproteins type A and B

“…Besides JUNV, other arenaviruses such as Lassa, Machupo, Guanarito and Sabiá viruses also cause severe haemorrhagic diseases in man. Specific rodents are the principal hosts of the arenaviruses and humans may become infected through direct contact with infected rodents or through inhalation of infectious rodent excreta and secreta (Charrel & de Lamballerie, 2010;Yun et al, 2008).…”

“…Besides JUNV, other arenaviruses such as Lassa, Machupo, Guanarito and Sabiá viruses also cause severe haemorrhagic diseases in man. Specific rodents are the principal hosts of the arenaviruses and humans may become infected through direct contact with infected rodents or through inhalation of infectious rodent excreta and secreta (Charrel & de Lamballerie, 2010;Yun et al, 2008).JUNV establishes a persistent infection in its main reservoir in nature, the cricetid Calomys musculinus, or in cell cultures (Ellenberg et al, 2002(Ellenberg et al, , 2004(Ellenberg et al, , 2007. Persistent infection in Vero cells is achieved after the acute phase of infection, which is characterized by the production of high titres of infectious virus and a marked cytopathic effect.…”

Functional Interferon System Is Required for Clearance of Lassa Virus

“…Nonhuman primates and guinea pigs are two most commonly used animal models of LF (2,6,7,12,15). However, the use of these animal models is often associated with high costs, limited availability, and handling-safety risks.…”

“…In order to assess the spread of LASV into the visceral organs and brains of infected mice, we humanely euthanized and necropsied three mice in each group and the titers of infectious virus in organ homogenates were analyzed by plaque assay (15). Both IFNAR Ϫ/Ϫ mice lacking the type I IFN receptor and IFN-a/ bgR Ϫ/Ϫ mice lacking type I/II IFN receptors developed disseminated infection by day 11 p.i.…”

Molecular Attenuation Process in Live Vaccine Generation for Arenaviruses

“…There are only two other Junín virus strains whose genome was fully sequenced, Romero and MC2 strains. Romero strain, classified as a high virulence strain, was isolated from an AHF patient and was passed twice in fetal rhesus lung cells and once in Vero cells (McKee et al, 1985;Yun et al, 2008). This strain is named Rumero in Genebank, but this was derived from a typographical mistake.…”