The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice

Abstract

SUMMARYThe pathogenicity for mice of two mutants of herpes simplex virus (type 1 and type 2), which fail to induce thymidine kinase, were compared with their respective parent strains. The mutants were much less virulent than the parents following either intracerebral or peripheral inoculation. The replication of the virus at the site ofinoculation and its progression into the nervous system were studied. Following a very large inoculum in the ear, the type 1 mutant was found to establish a latent infection in the cervical dorsal root ganglia. Mice inoculated intracerebrally with small doses of the mutant viruses were solidly immune to challenge with lethal doses of the parent strain.

Molecular Analysis of the Pyrimidine Deoxyribonucleoside Kinase Gene of Wild-type and Acyclovir-resistant Strains of Varicella-Zoster Virus

“…28 % amino acid sequence homology with the VZV dPK, and neither enzyme is essential for virus replication in vitro. These enzymes are, however, important for the activation of certain antiviral drugs (Elion et al, 1977) and may be important in the pathogenesis of infection (Field & Wildy, 1978;Tenser & Dunstan, 1979). The most effective antiviral agent currently available for VZV infections is the guanosine analogue acyclovir, which is phosphorylated preferentially by the VZV dPK.…”

Recombinant Viral Vector Vaccines for the Veterinary Use.

“…Viral proteins known to be involved in the virulence of herpesviruses are a class of enzymes that function at the level of DNA synthesis; the thymidine kinase (TK), ribonuclease reductase, and dUTPase [14,25,91]. A protein kinase encoded in the unique short (Us) region also appears to affect virulence at least in PRV [47,48].…”

“…TK, encoded in the genome of many herpesviruses, is not essential for virus growth in actively dividing tissue culture cells [25]. TK synthesized by alphaherpesviruses appears to facilitate the growth of virus in non-dividing cells [25].…”

“…TK synthesized by alphaherpesviruses appears to facilitate the growth of virus in non-dividing cells [25]. Many recent investigations have demonstrated that TK deficient mutants of herpes simplex virus type 1 (HSV-1) [25], PRV [49,112], BHV-1 [50], equine herpesvirus type 1 (EHV-1) [101], and FHV-1 [131] are remarkably attenuated for their natural hosts or mice and appear to be less readily reactivated from neurons [21]. Kit et al reported the loss of ability of BHV-1 TK deficient mutant to infect the fetus and to cause abortions [51] and the reduction of ability of the mutant to develop latent infections [50].…”

A Variant of Herpes Simplex Virus Type 2 Strain HG52 with a 1.5 kb Deletion in RL between 0 to 0.02 and 0.81 to 0.83 Map Units Is Non-neurovirulent for Mice

“…Mutation in or deletion of the viral thymidine kinase (TK) gene has been shown to impair virulence (Field & Wildy, 1978) and viral sequences between 0-7 and 0.83 map units (m.u.) have been shown to be involved in determining the virulence phenotype (Thompson & Stevens, 1983;Thompson et al, 1985 ;Javier et al, 1986;Rosen et al, 1986).…”