Immunosuppression-induced susceptibility of inbred hamsters (Mesocricetus auratus) to lethal-disease by lymphocytic choriomeningitis virus infection

Abstract

The role of the immune response in the pathogenesis of lethal and non-lethal lymphocytic choriomeningitis virus (LCMV)-infections of young adult Syrian golden hamsters (Mesocricetus auratus) of different strains was examined using immunosuppressive treatment with cyclophosphamide or with whole-body gamma-irradiation. In all hamsters, the LCMV strains, WE and Armstrong (ARM), caused systemic infections and induced comparable serum LCMV-antibody titers. However, lethal wasting-disease occurred which was hamster-strain and virus-strain dependent. With WE-inocula, MHA and PD4 inbred hamsters were all susceptible to lethal-disease and failed to completely eliminate infection. All LSH and CB inbred hamsters resisted lethal-disease and totally cleared WE-infection. Random colony-bred LVG hamsters and inbred LHC hamsters were intermediate in WE-susceptibility; some died with wasting, while others survived with minimal to no illness. ARM was avirulent for all hamsters and infections were totally cleared. By immunosuppressive treatment, all hamsters were rendered completely susceptible to lethal-disease by WE, and had unresolved infections and diminished serum LCMV-antibody titers. Immunosuppression also rendered all hamster strains partially susceptible to lethal infection by ARM. The hamster immune response was thus shown to suppress LCMV-infection and protect against lethal illness.

A Lethal Disease Model for Hantavirus Pulmonary Syndrome in Immunosuppressed Syrian Hamsters Infected with Sin Nombre Virus

“…Cyclophosphamide has been used to create viral disease models in multiple rodent species, including Syrian hamsters (20,21,(32)(33)(34)(35)(36)(37). Cyclophosphamide is an alkylating agent which intercalates into the DNA of actively dividing cells, causing apoptosis resulting in lymphopenia, suppressed B cell activity and activation, suppressed regulatory T cell function, neutropenia, and decreases in macrophage and dendritic cell numbers (14-17, 38, 39).…”

“…Dexamethasone is a glucocorticosteroid that acts as an immunosuppressant by interfering with NF-B-dependent gene activation, inhibiting lymphocyte proliferation, and reducing inflammatory responses by reducing proinflammatory gene expression and inducing anti-inflammatory genes (18). Both cyclophosphamide and dexamethasone have been used as immunosuppressive agents to alleviate or create disease in animal models of infectious diseases, namely, West Nile virus (19), severe acute respiratory syndrome (SARS) (20), lymphocytic choriomeningitis virus (21), and adenovirus (22).…”

An immunosuppressed Syrian golden hamster model for SARS-CoV infection

“…Cyclophosphamide, a bifunctional alkylating agent, has been shown to cause lymphopenia, suppress B-cell activity and activation, and suppress regulatory T-cell function (Cupps, et al, 1982; Ikezawa et al, 2005; Polak and Turk, 1974; Zhu et al, 1987). CP has been utilized in various animal models for virus infection analysis, often increasing the morbidity and mortality observed in virus-infected animals (Blandford and Charlton, 1977; Genovesi and Peters, 1987; Kercher and Mitchell, 2000; Kong et al, 2005; Mateo et al, 2006; Sidwell et al, 2003; Smee et al, 1991). Recently, CP-induced immunosuppression of Syrian golden hamsters was shown to enhance adenovirus replication and pathology, and permitted the efficacy testing of a broad-spectrum antiviral, CMX001 (Toth et al, 2008).…”