Central neuropathogenesis of vesicular stomatitis virus infection of immunodeficient mice

Abstract

To determine whether central neuropathogenesis associated with vesicular stomatitis virus (VSV) infection is regulated by T cells, we have examined the effects of intranasal infection of mice lacking T cells. The mice examined were of two kinds: (i) thymus-deficient BALB/c nulnu nice and (ii) BALB/c mice experimentally depleted of T cells by systemic infusions of a monoclonal antibody to the CD4 or CD8 cell surface molecules. These mice were infected intranasally with a single dose of replication-competent VSV. Brain tissue homogenates were analyzed for the presence of infectious virus. For each population of mice, infection-related mortality was assessed. In histological sections of brain, the distribution of viral antigens (Ags) was examined by immunocytochemistry. We found that recovery of infectious virus from homogenates of tissues obtained from athymic nulnu animals was more than 10 times greater than that from samples from their euthymic littermates. With a single exception in a BALB/c nulnu mouse, virus was not isolated from the spleen when it was administered intranasally. In these experimental infections, athymic mice succumbed 1 to 2 days before their euthymic littermates. A dose of virus that resulted in half of the nu/+ survival rate was uniformly lethal * Corresponding author.

In vivo biodistribution of a highly attenuated recombinant vesicular stomatitis virus expressing HIV-1 Gag following intramuscular, intranasal, or intravenous inoculation

“…While mice are not considered a natural host for VSV, they have been used as an animal model for studying VSV pathogenesis for over 70 years [38]. The exquisite sensitivity of mice to VSV infection has proven them as a valuable research tool for assessing virulence of wild type and attenuated strains of VSV [12][13][14][15][16][17][18][19][20]. While the neurovirulence associated with VSV infection in mice has been well studied, there has not been much advancement in the understanding of the biodistribution of VSV in mice since the pioneering work of Sabin and Olitsky in the 1930s [39][40][41][42][43].…”

“…VSV infection of humans is typically either asymptomatic or causes a mild influenza-like illness [6]. Among small mammals, mice are readily infected experimentally via a variety of inoculation routes and thus have served as a tractable model for immunogenicity, pathogenicity, neurotropism and neurovirulence studies [12][13][14][15][16][17][18][19][20].…”

Yellow Fever Virus Encephalitis: Properties of the Brain-Associated T-Cell Response during Virus Clearance in Normal and Gamma Interferon-Deficient Mice and Requirement for CD4+Lymphocytes

“…Infiltration of CD4 ϩ and CD8 ϩ T cells into the CNS has been observed in various models of neurotropic virus infection in rodents (6,11,42,46,73). It has been stated that in general, CD4 ϩ cells largely determine the protective immune response to viral infection of the brain (62), although a role for CD8 ϩ cells has been documented in some cases (6,21,28,65,72). It is also known that T cells can generate an immunopathologic response, depending on the type of infecting virus, (57,66,71).…”

Unraveling the functions of plasmacytoid dendritic cells during viral infections, autoimmunity, and tolerance

“…In contrast, we observed that the absence of pDCs resulted in a moderate but significant decrease in the numbers of OVA-specific CD8 + T cells, whereas the generation of plasma cells and production of virus-specific antibodies were unaffected. Although the reduction in antigen-specific CD8 + T cells had a modest impact on viral titers and survival, previously published data have illustrated that antibody responses are necessary and sufficient for VSV eradication, whereas a CTL response is not essential for VSV clearance but provides limited help to control viral spread (119).…”