scholarly journals Interferon Regulatory Factor 3-Dependent Pathways Are Critical for Control of Herpes Simplex Virus Type 1 Central Nervous System Infection

2010 ◽  
Vol 84 (19) ◽  
pp. 9685-9694 ◽  
Author(s):  
Vineet D. Menachery ◽  
Tracy Jo Pasieka ◽  
David A. Leib
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infection ◽  
Central Nervous System Infection ◽  
Regulatory Factor ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The initiation of the immune response at the cellular level relies on specific recognition molecules to rapidly signal viral infection via interferon (IFN) regulatory factor 3 (IRF-3)-dependent pathways. The absence of IRF-3 would be expected to render such pathways inoperative and thereby significantly affect viral infection. Unexpectedly, a previous study found no significant change in herpes simplex virus (HSV) pathogenesis in IRF-3−/− mice following intravenous HSV type 1 (HSV-1) challenge (K. Honda, H. Yanai, H. Negishi, M. Asagiri, M. Sato, T. Mizutani, N. Shimada, Y. Ohba, A. Takaoka, N. Yoshida, and T. Taniguchi, Nature 434:772-777, 2005). In contrast, the present study demonstrated that IRF-3−/− mice are significantly more susceptible to HSV infection via the corneal and intracranial routes. Following corneal infection with 2 × 106 PFU of HSV-1 strain McKrae, 50% of wild-type mice survived, compared to 10% of IRF-3-deficient mice. Significantly increased viral replication and inflammatory cytokine production were observed in brain tissues of IRF-3−/− mice compared to control mice, with a concomitant deficit in production of both IFN-β and IFN-α. These data demonstrate a critical role for IRF-3 in control of central nervous system infection following HSV-1 challenge. Furthermore, this work underscores the necessity to evaluate multiple routes of infection and animal models in order to fully determine the role of host resistance factors in pathogenesis.

scholarly journals Involvement of Apolipoprotein E in the Hematogenous Route of Herpes Simplex Virus Type 1 to the Central Nervous System

2002 ◽  
Vol 76 (23) ◽  
pp. 12394-12398 ◽  
Author(s):  
Javier S. Burgos ◽  
Carlos Ramirez ◽  
Isabel Sastre ◽  
María J. Bullido ◽  
Fernando Valdivieso
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Type ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
Hematogenous Route ◽  
Hsv 1

ABSTRACT Apolipoprotein E (ApoE), a constituent of the lipoproteins, may be relevant in herpes simplex virus type 1 (HSV-1) infection of the central nervous system (CNS), since HSV-1 binds to human serum ApoE lipoproteins. This study demonstrates the involvement of ApoE in the hematogenous route of HSV-1 to the CNS.

scholarly journals 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

2011 ◽  
Vol 18 (8) ◽  
pp. 1336-1342 ◽  
Author(s):  
Anna Grahn ◽  
Marie Studahl ◽  
Staffan Nilsson ◽  
Elisabeth Thomsson ◽  
Malin Bäckström ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Igg Antibodies ◽  
Herpes Simplex Virus 1 ◽  
Glycoprotein E ◽  
Varicella Zoster ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTHerpes 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.

scholarly journals Effect of Apolipoprotein E on the Cerebral Load of Latent Herpes Simplex Virus Type 1 DNA

2006 ◽  
Vol 80 (11) ◽  
pp. 5383-5387 ◽  
Author(s):  
Javier S. Burgos ◽  
Carlos Ramirez ◽  
Isabel Sastre ◽  
Fernando Valdivieso
Keyword(s):  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Herpes Simplex Virus Type ◽  
Acute Infection ◽  
Wild Type ◽  
Simplex Virus ◽  
The Brain ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) is neurotropic and enters a latent state lasting the lifetime of the host. This pathogen has recently been proposed as a risk factor for Alzheimer's disease (AD) in conjunction with apolipoprotein E4 (ApoE4). In a murine acute infection model, we showed that viral neuroinvasiveness depends directly on the overall ApoE dosage and especially on the presence of isoform ApoE4. If an interaction between ApoE and HSV-1 is involved in AD, it may occur during latency rather than during acute infection. Certainly, ApoE plays an important role in late-onset AD, i.e., at a time in life when the majority of people harbor HSV-1 in their nervous system. In the present work, wild-type, APOE knockout, APOE3, and APOE4 transgenic mice were used to analyze the influence of the ApoE profile on the levels of latent virus DNA. The knockout mice had significantly lower concentrations of the virus in the nervous system than the wild-type mice, while the APOE4 mice had very high levels in the brain compared to the APOE3 animals. ApoE4 seems to facilitate HSV-1 latency in the brain much more so than ApoE3. The APOE dosage correlated directly with the HSV-1 DNA concentration in the brain, strengthening the hypothesis that HSV-1, together with ApoE, might be involved in AD.

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