Complement-fixing reactivity of Varicella-Zoster virus subunit antigens with sera from homotypic infections and heterotypic Herpes simplex virus infections

Abstract

Various subunit antigens of varicella-zoster (V-Z) virus were examined for complement-fixing (CF) activity with sera from homotypic infections and from herpes simplex virus (HSV) infections in which a CF antibody titer rise was demonstrated with crude V-Z antigen. The subunit antigens included nucleocapsids, envelopes, a soluble antigen produced from infected culture fluids by sucrose density gradient centrifugation, a soluble antigen produced by reducing the volume of clarified infected culture fluids, a soluble antigen derived from infected cell lysates, a "viral" antigen consisting largely of enveloped particles with a few nucleocapsids, and a cell membrane-associated antigen. None was more suitable than crude V-Z antigen for serodifferentiation of V-Z virus and HSV infections. The envelope antigen, cell membrane antigen, and the soluble antigen prepared by density gradient centrifugation showed little reactivity with sera from varicella and HSV infections, but gave high antibody titers with sera from zoster infections, suggesting that a secondary V-Z virus infection is required to produce an antibody response to these subunit antigens. Patients with varicella and zoster infections and the selected patients with HSV infections all showed significant CF antibody responses to the other V-Z subunit antigens.It is well established that infection with herpes simplex virus (HSV) may elicit heterotypic antibody responses to varicella-zoster (V-Z) virus in individuals who have experienced a previous V-Z virus infection (3,8,9,11). Differential serological diagnosis of HSV and V-Z virus infections may be hampered by these heterotypic antibody responses, which are demonstrable by fluorescent-antibody staining and neutralization tests (8,9) as well as by complement fixation (CF) tests (3,9,11).Martin and Palmer (5) reported that a cellfree soluble CF antigen derived from V-Z virusinfected cell cultures failed to show heterotypic reactivity with sera from HSV patients who showed CF antibody titer rises with crude V-Z antigens, and suggested that such soluble V-Z CF antigens might be useful in the differential serological diagnosis of HSV and V-Z virus infections. The present studies were undertaken to explore further the CF reactivity of subunit antigens of V-Z virus with sera from homotypic infections and from HSV infections, and to assess the usefulness of soluble V-Z antigens for serological differentiation of HSV and V-Z virus infections. MATERIALS AND METHODSPreparations of CF antigens. The Batson strain of V-Z virus (10) and the L 645 strain of human fetal diploid lung (HFDL) cells, established by J. H. Schieble of this laboratory, were used for preparation of V-Z virus antigens. Infected HFDL cells in a 29-oz (ca. 800-ml) culture bottle which showed a 2+ viral cytopathic effect were dispersed with trypsin and used to infect six roller bottle cultures of HFDL cells; these were maintained on Eagle minimal essential medium supplemented with 2% inactivated fetal bovine serum. Cultures were harvested after 4 days of inc...

Human serum antibodies to varicella-zoster virus thymidine kinase

“…We also examined sera from atypical herpes zoster patients, consisting of individuals with symptoms which could be caused by HSV as well as VZV. The CF titers were of limited diagnostic value, and two persons in this group exhibited titer conversions for both HSV and VZV (16,26,27). The occurrence of VZV dTkblocking antibodies in serum from two patients in this category indicates that the dTk-blocking antibody assay could be of value in the diagnosis of atypical herpes zoster.…”

“…VZV dTk AND H tion with primary VZV infections, the antibody response is directed primarily against the nucleocapsid antigen, whereas in herpes zoster a broader antibody response to envelope and soluble antigens is apparent (26).…”

Detection of both herpes simplex and varicella‐zoster viruses in cerebrospinal fluid from patients with encephalitis

“…When tests for HSV IgG and VZV IgG antibody were performed in CSF, the finding of results suggesting intrathecal production of specific antibody to both agents was not unusual IEchevarria et al, 1990bl. Such findings were mainly interpreted as reflecting either cross-reactivity through epitopes common to HSV and VZV antigens or heterotypic responses after polyclonal B-cell activation [Schmidt et al, 1977;Forsgren et al, 1989;Denin and Herb, 1989;Mathiessen et al, 1989;Roberg et al, 19951. However, dual infections, due to concomitant recurrence of both viruses toward the CNS, cannot be excluded as an explanation [Echevarria et al, 1990al. In recent years, the polymerase chain reaction (PCR) assay has proven to be a powerful tool for detecting a broad range of infectious agents which can be present in extremely small amounts in human tissues or body fluids.…”

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

“…Direct diagnosis has been performed by immunodiffusion (15) and immunofluorescence (11). Serological diagnosis of VZV often is hampered by heterologous antibody response against HSVs (12,13).…”