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. 2011 Aug;18(8):1336-42.
doi: 10.1128/CVI.05061-11. Epub 2011 Jun 22.

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

Anna Grahn  1 , Marie Studahl, Staffan Nilsson, Elisabeth Thomsson, Malin Bäckström, Tomas Bergström
Affiliations

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

Anna Grahn et al. Clin Vaccine Immunol. 2011 Aug.

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.

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Figures

Fig. 1.
Fig. 1.
OD levels at different time points of IgG analysis by ELISA of CSF (A and B) and serum (C and D) samples from 15 patients with VZV CNS infection and 14 patients with HSE. The IgG response was analyzed with whole-VZV antigen versus VZV gE antigen. All samples of serum and CSF were diluted to an identical concentration of total IgG (1 μg/ml).
Fig. 2.
Fig. 2.
Intrathecal antibody production illustrated by the CSF/serum OD ratios at 15 min (A) and at Vmax (B) of 15 VZV patients with CNS infection and 14 patients with HSE. The total IgG in serum and CSF samples is diluted to identical concentrations (1 μg/ml) in all samples and analyzed with VZV gE antigen versus whole-virus antigen by ELISA. The paired t test was used for analysis between VZV gE and whole-VZV antigen. Significantly higher CSF/serum OD ratios were found in the VZV patients at both 15 min and at Vmax using VZV gE antigen. In the HSE patients, the CSF/serum OD ratios were significantly lower using VZV gE antigen at both 15 min and at Vmax.
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