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 Fatal Multiorgan Failure Associated with Disseminated Herpes Simplex Virus-1 Infection: A Case Report

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Michael Glas ◽  
Sigrun Smola ◽  
Thorsten Pfuhl ◽  
Juliane Pokorny ◽  
Rainer M. Bohle ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Multiorgan Failure ◽  
Acute Infection ◽  
B Cell Lymphoma ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus type 1 (HSV-1) infections cause typical dermal and mucosal lesions in children and adults. Also complications to the peripheral and central nervous system, pneumonia or hepatitis are well known. However, dissemination to viscera in adults is rare and predominantly observed in immunocompromised patients. Here we describe the case of a 70-year-old male admitted with macrohematuria and signs of acute infection and finally deceasing in a septic shock with multi organ failure 17 days after admission to intensive care unit. No bacterial or fungal infection could be detected during his stay, but only two days before death the patient showed signs of rectal, orolabial and genital herpes infection. The presence of HSV-1 was detected in swabs taken from the lesions, oropharyngeal fluid as well as in plasma. Post-mortem polymerase chain reaction analyses confirmed a disseminated infection with HSV-1 involving various organs and tissues but excluding the central nervous system. Autopsy revealed a predominantly retroperitoneal diffuse large B-cell lymphoma as the suspected origin of immunosuppression underlying herpes simplex dissemination.

scholarly journals Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Yike Jiang ◽  
Chaya D. Patel ◽  
Richard Manivanh ◽  
Brian North ◽  
Iara M. Backes ◽  
...  
Keyword(s):  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Neural Tissue ◽  
Maternal Antibodies ◽  
Herpes Simplex Virus 1 ◽  
Maternal Immunization ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization. IMPORTANCE Herpes simplex virus 1 is a common infection of the nervous system that causes devastating neonatal disease. Using mouse and human tissue, we discovered that antiviral antibodies accumulate in neural tissue after HSV-1 infection in adults. Similarly, these antibodies pass to the offspring during pregnancy. We found that antiviral maternal antibodies can readily access neural tissue of the fetus and neonate. These maternal antibodies then protect neonatal mice against HSV-1 neurological infection and death. These results underscore the previously unappreciated role of maternal antibodies in protecting fetal and newborn nervous systems against infection. These data suggest that maternal immunization would be efficacious at preventing fetal/neonatal neurological infections. IMPORTANCE Herpes simplex virus 1 is a common infection of the nervous system that causes devastating neonatal disease. Using mouse and human tissue, we discovered that antiviral antibodies accumulate in neural tissue after HSV-1 infection in adults. Similarly, these antibodies pass to the offspring during pregnancy. We found that antiviral maternal antibodies can readily access neural tissue of the fetus and neonate. These maternal antibodies then protect neonatal mice against HSV-1 neurological infection and death. These results underscore the previously unappreciated role of maternal antibodies in protecting fetal and newborn nervous systems against infection. These data suggest that maternal immunization would be efficacious at preventing fetal/neonatal neurological infections.

scholarly journals Frequency and Abundance of Alphaherpesvirus DNA in Human Thoracic Sympathetic Ganglia

2014 ◽  
Vol 88 (14) ◽  
pp. 8189-8192 ◽  
Author(s):  
Maria A. Nagel ◽  
April Rempel ◽  
Jonathon Huntington ◽  
Forrest Kim ◽  
Alexander Choe ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Varicella Zoster Virus ◽  
Sympathetic Ganglia ◽  
Herpes Simplex Virus 1 ◽  
Varicella Zoster ◽  
Target Organs ◽  
Simplex Virus ◽  
Visceral Disease ◽  
Hsv 1

Alphaherpesvirus reactivation from thoracic sympathetic ganglia (TSG) and transaxonal spread to target organs cause human visceral disease. Yet alphaherpesvirus latency in TSG has not been well characterized. In this study, quantitative PCR detected varicella-zoster virus (VZV), herpes simplex virus 1 (HSV-1), and HSV-2 DNA in 117 fresh TSG obtained postmortem from 15 subjects. VZV DNA was found in 76 (65%) ganglia from all subjects, HSV-1 DNA was found in 5 (4%) ganglia from 3 subjects, and no HSV-2 was found.

scholarly journals Role of the DNA Sensor STING in Protection from Lethal Infection following Corneal and Intracerebral Challenge with Herpes Simplex Virus 1

2015 ◽  
Vol 89 (21) ◽  
pp. 11080-11091 ◽  
Author(s):  
Zachary M. Parker ◽  
Aisling A. Murphy ◽  
David A. Leib
Keyword(s):  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Host Protein ◽  
Herpes Simplex Virus 1 ◽  
Infection Route ◽  
Antiviral State ◽  
Mucosal Infection ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTSTING is a protein in the cytosolic DNA and cyclic dinucleotide sensor pathway that is critical for the initiation of innate responses to infection by various pathogens. Consistent with this, herpes simplex virus 1 (HSV-1) causes invariable and rapid lethality in STING-deficient (STING−/−) mice following intravenous (i.v.) infection. In this study, using real-time bioluminescence imaging and virological assays, as expected, we demonstrated that STING−/−mice support greater replication and spread in ocular tissues and the nervous system. In contrast, they did not succumb to challenge via the corneal route even with high titers of a virus that was routinely lethal to STING−/−mice by the i.v. route. Corneally infected STING−/−mice also showed increased periocular disease and increased corneal and trigeminal ganglia titers, although there was no difference in brain titers. They also showed elevated expression of tumor necrosis factor alpha (TNF-α) and CXCL9 relative to control mice but surprisingly modest changes in type I interferon expression. Finally, we also showed that HSV strains lacking the ability to counter autophagy and the PKR-driven antiviral state had near-wild-type virulence following intracerebral infection of STING−/−mice. Together, these data show that while STING is an important component of host resistance to HSV in the cornea, its previously shown immutable role in mediating host survival by the i.v. route was not recapitulated following a mucosal infection route. Furthermore, our data are consistent with the idea that HSV counters STING-mediated induction of the antiviral state and autophagy response, both of which are critical factors for survival following direct infection of the nervous system.IMPORTANCEHSV infections represent an incurable source of morbidity and mortality in humans and are especially severe in neonatal and immunocompromised populations. A key step in the development of an immune response is the recognition of microbial components within infected cells. The host protein STING is important in this regard for the recognition of HSV DNA and the subsequent triggering of innate responses. STING was previously shown to be essential for protection against lethal challenge from intravenous HSV-1 infection. In this study, we show that the requirement for STING depends on the infection route. In addition, STING is important for appropriate regulation of the inflammatory response in the cornea, and our data are consistent with the idea that HSV modulates STING activity through inhibition of autophagy. Our results elucidate the importance of STING in host protection from HSV-1 and demonstrate the redundancy of host protective mechanisms, especially following mucosal infection.

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.

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