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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

Journal article
Authors Anna Grahn
Marie Studahl
Staffan Nilsson
Elisabeth Thomsson
Malin Bäckström
Tomas Bergström
Published in Clinical and Vaccine Immunology
Volume 18
Issue 8
Pages 1336-1342
ISSN 1556-6811
Publication year 2011
Published at Department of Mathematical Sciences, Mathematical Statistics
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Institute of Biomedicine, Department of Infectious Medicine
Pages 1336-1342
Language en
Links dx.doi.org/10.1128/CVI.05061-11
Keywords polymerase-chain-reaction, cerebrospinal-fluid, clinical-manifestations, complement-fixation, encephalitis, gb, neutralization, purification, disease, adults
Subject categories Microbiology in the medical area, Infectious Medicine

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. Biosynthesis of ethylene (ethene) is mainly performed by plants and some bacteria and fungi, via two distinct metabolic routes. Plants use two steps, starting with S-adenosylmethionine, while the ethylene-forming microbes perform an oxygen dependent reaction using 2-oxoglutarate and arginine. Introduction of these systems into Saccharomyces cerevisiae was studied in silico. The reactions were added to a metabolic network of yeast and flux over the two networks was optimised for maximal ethylene formation. The maximal ethylene yields obtained for the two systems were similar in the range of 7-8 mol ethylene/10 mol glucose. The microbial metabolic network was used for testing different strategies to increase the ethylene formation. It was suggested that supplementation of exogenous proline, using a solely NAD-coupled glutamate dehydrogenase, and using glutamate as the nitrogen source, could increase the ethylene formation. Comparison of these in silico results with published experimental data for yeast expressing the microbial system confirmed an increased ethylene formation when changing nitrogen source from ammonium to glutamate. The theoretical analysis methods indicated a much higher maximal yield per glucose for ethylene than was experimentally observed. However, such high ethylene yields could only be obtained with a concomitant very high respiration (per glucose). Accordingly, when ethylene production was optimised under the additional constraint of restricted respiratory capacity (i.e. limited to experimentally measured values) the theoretical maximal ethylene yield was much lower at 0.2/10 mol glucose, and closer to the experimentally observed values.

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