Biochemical Transformation of Mouse Cells by Varicella-Zoster Virus

Abstract

SUMMARYMouse L cells lacking the enzyme thymidine kinase (Ltk-) were infected with varicella-zoster virus (VZV). Even though virus did not replicate in Ltk-cells, the presence of virus antigen could be observed by use of an anti-complement immunofluorescent technique at 4 h post-infection and the VZV-specific thymidine kinase could be detected in VZV-infected Ltk-cells. Ltk-cells were converted to a tk + phenotype (Ltk +) by infection with cell-associated VZV. Clones possessing the ability to grow in selective medium were isolated and cultured successfully for more than 20 passages. One of the clones grew very slowly, but other clones showed almost the same growth rate as that of the parental Ltk-cells. The chromosome analyses of Ltk-cells and transformed cells revealed that the isolated clones were of mouse origin. VZV-specific antigen could be detected in the nuclei of Ltk + cell clones by an immunofluorescent test, while tk activity was greatly enhanced in extracts prepared from transformed cells and its activity was neutralized by hyperimmune serum against VZV.

Mapping of the varicella zoster virus deoxypyrimidine kinase gene and preliminary identification of its transcript

“…VZV is also known to induce an enzyme with dPK activity in infected cells (Dobersen et al, 1976;Ogino et al, 1977;Hackstadt and Mallavia, 1978;Cheng et aZ., 1979), and cell-associated VZV has been used to biochemically transform LTK-cells (Yamanishi et al, 1981). Studies of dPK activity in VZV-infected cells suggest that this activity is associated with a 35,000 MW polypeptide that may exist as a 70,000 MW protein composed of nearly identical subunits (Lopetegui et al, 1983;Shiraki et al, 1985).…”

Varicella-Zoster Virus-Induced Transformation of Mammalian Cells in Vitro.

“…Hamsters bearing VZVinduced tumors also develop VZV-specific antibodies [17]. Finally, varicella-zoster virus has also been shown to biochemically transform thymidine kinase-negative cells to a tk"^ phenotype [16].…”

“…VZV, like other human herpesviruses, establishes latent infection [15]. VZV, like HSV, is able to biochemically transform thymidine kinase-negative cells to a thymidine kinase-positive phenotype [16]. In addition, VZV is also able to transform mammalian cells in vitro [17].…”

Immunochemical Characterization of Pyrimidine Kinase Induced by Varicella-Zoster Virus

“…From studies on biochemically transformed cells, Kit et al (1980a, b) speculated that herpesvirusassociated nuclear antigen(s) (HANA) and HSV type 1 TK are identical or closely related. Yamanishi et al (1981) detected nuclear fluorescence with anti-VZV serum in VZV biochemically transformed mouse cells. Our observation of the localization of TK in nuclei of infected cells is consistent with these findings on biochemically transformed cells.…”