Varicella-Zoster Virus (VZV) Glycoprotein E Is a Serological Antigen for Detection of Intrathecal Antibodies to VZV in Central Nervous System Infections, without Cross-Reaction to Herpes Simplex Virus 1

Abstract

Herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) cause serious central nervous system (CNS) diseases that are diagnosed with PCR using samples of cerebrospinal fluid (CSF) and, during later stages of such infections, with assays of intrathecal IgG antibody production. However, serological diagnoses have been hampered by cross-reactions between HSV-1 and VZV IgG antibodies and are commonly reported in patients with herpes simplex encephalitis (HSE). In this study we have evaluated VZV glycoprotein E (gE) as a new antigen for serological diagnosis of VZV-induced CNS infections. Paired samples of CSF and serum from 29 patients with clinical diagnosis of VZV CNS infection (n ‫؍‬ 15) or HSE (n ‫؍‬ 14), all confirmed by PCR, were analyzed. VZV gE and whole VZV were compared as antigens in enzyme-linked immunosorbent assays (ELISAs) for serological assays in which the CSF/serum sample pairs were diluted to identical IgG concentrations. With the gE antigen, none of the HSE patients showed intrathecal IgG antibodies against VZV, compared to those shown by 11/14 patients using whole-VZV antigen (P < 0.001). In the patients with VZV infections, significantly higher CSF/serum optical density (OD) ratios were found in the VZV patients using the VZV gE antigen compared to those found using the whole-VZV antigen (P ‫؍‬ 0.001). These results show that gE is a sensitive antigen for serological diagnosis of VZV infections in the CNS and that this antigen was devoid of cross-reactivity to HSV-1 IgG in patients with HSE. We therefore propose that VZV gE can be used for serological discrimination of CNS infections caused by VZV and HSV-1.

Changes to anti-JCV antibody levels in a Swedish national MS cohort

“…A recently published ELISA to determine OD values for highly specific IgG-antibodies against a recombinant VZV glycoprotein E antigen produced in mammalian cells was used to study for anti-VZV antibodies, and paired samples were analysed on the same plate 19 20…”

Varicella-zoster virus infections of the central nervous system – Prognosis, diagnostics and treatment

“…Intrathecal antibodies against VZV have previously also been detected in HSE [120,121], interpreted as a cross-reactive phenomenon, but this problem has been overcome by a more specific serology based on glycoprotein VZV IgE as an antigen [122].…”

Cerebrospinal Fluid Abnormalities in Viral Encephalitis

“…VZV glycoprotein E does not express antigenic resemblance with the herpes simplex virus, and is easily determined with performing ELISA. This method has a high specifity and sensitivity for VZV encephalitis, it may also be utilised for the differential diagnosis with herpes virus [11]. The test to be choosen in Ebstein-Barr virus and in Citomegalovirus encephalitis is again PCR.…”