Comparison of central nervous system disease produced by wild-type and temperature-sensitive mutants of vesicular stomatitis virus

Abstract

The pathogenicity of infection produced following intracerebral (i.c.) inoculation of wild-type vesicular stomatitis virus (VSV) or temperature-sensitive (ts) mutants of VSV was compared. ts mutants used were ts 31 (VSV complementation group II) and ts 41 (VSV complementation group IV). The i.c. injection of wild-type VSV in weanling Swiss mice produced a rapidly fatal encephalitis with death of mice in 2 to 3 days. Histopathologically, such mice exhibited minimal changes of encephalitis on light microscopy. In contrast to the highly virulent, rapidly fatal central nervous system (CNS) infection seen after i.c. inoculation of wild-type VSV, infection with ts 31 VSV produced a more slowly progressive CNS infection characterized by hind limb paralysis and death 6 to 9 days after infection. Histopathologically, CNS infection with ts 31 is associated with previously unreported extensive spongiform changes in the gray matter of the spinal cord. The inoculation of ts 41 i.c., on the other hand, did not result in either clinical illness or histopathological changes in the spinal cords or brains of infected mice. The absence of clinical and histopathological lesions following i.c. infection ofts 41 VSV suggests that the capacity to alter the pathogenesis of VSV CNS infection may be a function of only certain ts mutants of VSV.

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

“…Reichmann (University of Illinois, Urbana, IL, U.S.A.) and has previously been described (Pringle, 1970;Reichmann et al, 1971). TsG31-KS5 VSV was a clonal isolate of tsG31 VSV that was plaque purified as described previously (Rabinowitz et al, 1976). Briefly, BHK-21 cells were cultured in 6-well plates (35 x 10 mm; Costar, Cambridge, MA, U.S.A.) in 2.0 ml of Dulbecco modified Eagle medium (DMEM) supplemented with 10% bovine calf serum (Hazelton Research Products, Lenexa, KS, U.S.A.).…”

“…The clones were grown in BHK-21 cells and plaque-purified a second time. The clones were then purified on sucrose gradients as described previously (Rabinowitz et al, 1976).…”

“…Infection of mice with virus has been previously described (Rabinowitz et al, 1976). Briefly, 5 x 104 plaque forming units (PFU) of tsG31-KS5 VSV in 30 /~1 of Hanks' balanced salt solution (HBSS) was injected into the frontal cerebral lobe of mice that had been lightly anesthetized with ether (Sigma Chemical Co., St. Louis, MO, U.S.A.) with a 27-gauge needle.…”

“…Common viruses and their variants, more frequently associated with acute clinical diseases, often produce prolonged clinical courses that are distinct from the more acute manifestations with the central nervous system (CNS) often providing the site for these persistent host-parasite relationships (Johnson, 1986). Viruses that have been associated with such relationships include measles (Horta-Barbosa et al, 1969), herpes simplex (Elizan et al, 1983), coronaviruses (Fishman et al, 1985), certain parvoviruses (Simpson et al, 1984), reovirus (Tyler et al, 1985), Theiler's encephalitis (Roos et al, 1982), vesicular stomatitis virus (VSV) (Rabinowitz et al, 1976;Dal Canto et al, 1979) and many others. How these persistent relationships are established and maintained is not precisely known, although it is generally thought that the properties of the viruses, the hosts' immune systems, and neuroendocrinological factors may be involved.…”

Immunohistochemical and behaviour pharmacological analysis of rats inoculated intranasally with vesicular stomatitis virus

“…A temperature-sensitive mutant of VSV, designated G41, was used in all experiments. The characteristics of this mutant have been described previously (Rabinowitz et al, 1976). The VSV strain was generously provided by Dr Mauro Dal Canto, Department of Pathology, Northwestern University, Illinois, USA.…”