Reconstitution with T Lymphocytes Protects Nude Mice from a Central Nervous System Disorder Induced by a Temperature-sensitive Vesicular Stomatitis Virus

Abstract

SUMMARYA temperature-sensitive mutant of vesicular stomatitis virus (VSV), tsG31-KS5 VSV, intracerebrally inoculated into BALB/c (+/+) or Swiss outbred mice yielded a clinically asymptomatic persistent infection of the central nervous system (CNS). BALB/c nude (nu/nu) mice infected with tsG31-KS5 VSV, however, all perished within 26 days of infection. All the nude mice were afflicted with a slowly progressing CNS disorder, with symptoms including lethargy, curvature of the spine, hind-limb paralysis and other neurological disorders, before they succumbed to the infection. Wild-type (wt) VSV infection of either normal or nude mice, on the other hand, invoked a rapidly lethal disease with all animals dying within 4 days of infection. When nude mice were reconstituted with 5 x 106 syngeneic T lymphocyte-enriched splenocytes, over 70% of them not only survived the tsG31-KS5 VSV infection but appeared to be free of any neurological disorders. Only 20 % of these reconstituted mice infected for 20 days with tsG31-KS5 VSV endured a wt VSV challenge. In contrast, BALB/c (+/+) mice infected for 20 days with tsG31-KS5

Central neuropathogenesis of vesicular stomatitis virus infection of immunodeficient mice

“…Therefore, we conclude that natural killer cells and the IFN-ot and -3 from non-T-cell sources do not provide protection sufficient to enable recovery in this model. This finding confirms results of earlier studies with VSV in which a cell population responsive to P-endorphin affords protection in T-cell-reconstituted BALB/c nu/lnu mice (6,8,9). We have additional data from adoptive transfer studies which demonstrate an essential role for T cells in promoting clearance of virus from brain and recovery from VSV infection (27).…”

β-Endorphin alters a viral induced central nervous system disease in normal mice but not in nude mice

“…When nude mice were reconstituted with T lymphocytes, 70% of the animals survived a tsG31-KS5 VSV infection. Neutralizing antibody against VSV did not appear to be involved in the protection, since many T lymphocyte-reconstituted nude mice did not have detectable levels of neutralizing antibody yet survived the infection without any signs of disease (Doll and Johnson, 1988). Interestingly, infectious VSV could be isolated from both nude mice that were reconstituted with T lymphocytes before infection and from nude mice only inoculated with tsG31-KS5 VSV, and the amount of infectious VSV being harbored in the CNS of the two groups of animals was equivalent (Doll and Johnson, 1989).…”

Viral Replication in Olfactory Receptor Neurons and Entry into the Olfactory Bulb and Braina

“…In the absence of a functionally intact immune system, a variety of defects in the hosts' response to intranasal VSV infection have been observedTable 2). Mice that do not have a functional T cell compartment (severe combined immunodeficiency (SCID) mice or nude mice) readily succumb to infection, even when the virus is administered parenterally 8‐10. In BALB/c‐H‐2 dm2 mice, which do not have the class I major histocompatibility complex (MHC‐I) restricting heterodimer, H‐2L d , the infection proceeds without significant differences from mice able to use CD8 + effector T cells; this shows that CD4 + T cells are sufficient at controlling the infection and promoting recovery of mice 3,6.…”