Neutralizing antibodies specific for glycoprotein H of herpes simplex virus permit viral attachment to cells but prevent penetration.

ABSTRACT Antibodies to herpes simplex virus type 1 (HSV-1) and HSV-2 of the immunoglobulin G (IgG) and IgA isotypes were detected in the cervicovaginal secretions (CVS) of 77 HSV-1- and HSV-2-seropositive but clinically asymptomatic African women by type-specific enhanced chemiluminescence Western blotting (ECL-WB). Of the 77 subjects, 34 were HIV negative, shedding HSV-2 DNA in their genital secretions; 20 were HIV positive, shedding HSV-2 DNA; and 23 were HIV negative, not shedding HSV-2 DNA. HSV-specific IgG was detected in CVS of nearly 70% of the women studied. HSV-specific IgA was found in CVS of 50% of the women studied. The distribution of CVS HSV-specific antibodies to each HSV type was highly heterogeneous, with a slight predominance of detectable IgG to HSV-1 (59%) over IgG to HSV-2 (41%), whereas the frequency of detectable IgA to HSV-1 (39%) was similar to that of IgA to HSV-2 (36%). The presence of detectable HSV-specific antibodies was inversely associated with HSV-2 DNA genital asymptomatic shedding but was not affected by HIV seropositivity. In addition, 13 of 77 (17%) CVS samples showed neutralizing activity against HSV-2, as assessed by an HSV-2 in vitro infectivity reduction assay. Neutralizing activity in CVS was associated with the presence of IgG and/or IgA antibodies to HSV-1 and/or to HSV-2 by ECL-WB. Among women whose CVS showed HSV-2-neutralizing activity, the specific activity of HSV-specific neutralizing antibodies was substantially (fivefold) higher in HSV-2 DNA shedders than in nonshedders. In conclusion, HSV-specific antibodies are frequently detected in CVS of asymptomatic African women seropositive for HSV-1 and HSV-2. A subset of these women had functional neutralizing activity against HSV-2 in their CVS. The origin of these antibodies and their role in HSV-2 disease of the female genital tract remain to be determined.

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Development of a high-throughput β-Gal-based neutralization assay for quantitation of herpes simplex virus-neutralizing antibodies in human samples

Vaccine ◽

10.1016/j.vaccine.2016.05.033 ◽

2016 ◽

Vol 34 (33) ◽

pp. 3901-3906 ◽

Cited By ~ 4

Author(s):

Amy Baccari ◽

Michael Cooney ◽

Tamara P. Blevins ◽

Lynda A. Morrison ◽

Shane Larson ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

High Throughput ◽

Neutralizing Antibodies ◽

Neutralization Assay ◽

Human Samples ◽

Simplex Virus

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Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization

Frontiers in Microbiology ◽

10.3389/fmicb.2021.799890 ◽

2022 ◽

Vol 12 ◽

Author(s):

Xiaowei Song ◽

Yiliang Wang ◽

Feng Li ◽

Wenyan Cao ◽

Qiongzhen Zeng ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Actin Polymerization ◽

Neuronal Cells ◽

Antiviral Drugs ◽

Hsp90 Inhibitors ◽

Herpes Simplex Virus 1 ◽

Viral Attachment ◽

Simplex Virus ◽

Hsv 1

Herpes simplex virus 1 (HSV-1) is a common neurotropic virus, the herpes simplex encephalitis (HSE) caused by which is considered to be the most common sporadic but fatal encephalitis. Traditional antiviral drugs against HSV-1 are limited to nucleoside analogs targeting viral factors. Inhibition of heat shock protein 90 (Hsp90) has potent anti-HSV-1 activities via numerous mechanisms, but the effects of Hsp90 inhibitors on HSV-1 infection in neuronal cells, especially in the phase of virus entry, are still unknown. In this study, we aimed to investigate the effects of the Hsp90 inhibitors on HSV-1 infection of neuronal cells. Interestingly, we found that Hsp90 inhibitors promoted viral adsorption but inhibited subsequent penetration in neuronal cell lines and primary neurons, which jointly confers the antiviral activity of the Hsp90 inhibitors. Mechanically, Hsp90 inhibitors mainly impaired the interaction between Hsp90 and cofilin, resulting in reduced cofilin membrane distribution, which led to F-actin polymerization to promote viral attachment. However, excessive polymerization of F-actin inhibited subsequent viral penetration. Consequently, unidirectional F-actin polymerization limits the entry of HSV-1 virions into neuron cells. Our research extended the molecular mechanism of Hsp90 in HSV-1 infection in neuron cells and provided a theoretical basis for developing antiviral drugs targeting Hsp90.

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