Human serum antibodies to varicella-zoster virus thymidine kinase

Abstract

The conditions required for the production of varicella-zoster virus (VSV)-induced deoxythymidine kinase (dTk) have been studied. Extracts from Vero cells harvested 62 h after VZV infection were found to contain VZV-induced dTk activity, with a minimal contribution from the cellular dTk activity. VZV dTK was shown to have a broad substrate specificity phosphorylating both deoxythymidine, deoxycytidine, and iododeoxyuridine. Deoxythymidine triphosphate inhibition studies revealed an intermediate deoxythymidine triphosphate sensitivity when compared with that of the cellular cytosolar enzyme and the deoxythymidine triphosphate-insensitive herpes simplex virus dTk. An assay for VZV dTk-blocking antibodies was developed, with [125I]iododeoxyuridine as a substrate in the presence of a deoxythymidine triphosphate concentration which selectively blocked the dTK of host cell origin. A total of 79 serum samples were studied; these included serum pairs from patients with varicella or herpes zoster and single sera from immune and nonimmune adults. VZV dTk blocking antibodies were detected exclusively in sera from patients with herpes zoster. All serum pairs showing VZV dTK seroconversion also showed a parallel conversion of complement fixation titers. The VZV dTk antibodies were found to be of the immunoglobulin G class. The immunological specificity of VZV dTK was investigated, and no cross-reactivity with herpes simplex virus type 1 or 2 dTk was found.

Application of an in vitro assay for serum thymidine kinase: Results on viral disease and malignancies in humans

“…We have previously described a sensitive TK assay and its potential use in clinical virology (Gronowitz and Kallander, 1980). The sensitivity of the TK assay and the fact that antisera exist which neutralize HSV TK in a types-specific manner makes it moreover possible to use a TK inhibition assay for direct typing of HSV isolates and vesicle fluid specimens (Gronowitz et al, 1982). In the present communication we describe an improved TK assay, applicable to the detection of TK activity in human serum, and the results indicate that s-TK may serve as avaluable marker in clinical medicine.…”

“…These values are in the same range as those previously reported for the purified human TK1 isozyme (dThd 2.6 X 10" M, IdUrd 2.4 X 10" M; Lee and Cheng, 1976). For the human TK2, the re orted IdUrd (Lee and Cheng, 1976) while the HSV TKs have K, values in the range 1.9-2.8 X lo-' for IdUrd and 4.6-6.6XlO-' for dThd (Gronowitz and Kallander, 1980) Our previously described assay has been used for detection of minute amounts of viral TK enzyme in specimens from patients with HSV infections (Gronowitz et al, 1982) and was also used for the detection of antibodies against HSV and varicella-zoster virus (VZV) TK in human serum (Gronowitz and Kailander, 1981;Kallander et al, 1982). When performing these antibody studies we found that a few sera, derived from patients with infectious mononucleosis (IM), contained high levels of TK activity.…”

Relationship between nasopharyngeal carcinoma and high antibody titers to epstein‐barr virus‐specific thymidine kinase

“…While accurate diagnosis and/or efficient chemotherapy methods were developing from the immunological and functional specificities of DNase and thymidine kinase (TK) activities induced by several human herpes viruses (Cheng et al, 1978(Cheng et al, , 1982Gronowitz et al, 1982;Kallander et al, 1982). we reached agreement with other authors on the existence of EBV-specific DNase (Tan et al, 19826;Ooka et al, 1984) and TK (Ooka ef al.. 1983;McGabhann er al., 1984;Littler et al, 1986Littler et al, , 1987de Turenne-Tessier er al., 1986).…”

Rapid diagnosis of varicella-zoster virus infection by detection of viral deoxythymidine kinase in serum and vesicle fluid

“…HSV dTk's are immunogenic, and antisera against the isozymes have been obtained by immunization of animals with extracts from infected or transformed cells (2,9,14). Antibodies against both HSV and VZV dTk are also present in human sera after viral infections (3,6,10). We have shown in a separate study that the dTk level in human serum in connection with infectious mononucleosis is elevated 10 to 40 times.…”

“…The assay measures residual enzyme activity after preincubation of vesicle fluid with HSV type 1 (HSV 1) or HSV type 2 (HSV 2) dTk antisera. Further studies of VZV dTk in infected cell cultures indicated high levels of enzyme activity (10). This prompted us to attempt direct detection of VZV dTk in clinical specimens to develop a general rapid typing method for VZV, HSV 1, and HSV 2 infections.…”