herpes simplex
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2022 ◽  
Author(s):  
Iara M Backes ◽  
Brook K Byrd ◽  
Chaya D Patel ◽  
Sean A Taylor ◽  
Callaghan R Garland ◽  
...  

Neonatal herpes simplex virus (HSV) infections often result in significant mortality and neurological morbidity despite antiviral drug therapy. Maternally-transferred HSV-specific antibodies reduce the risk of clinically-overt neonatal HSV (nHSV), but this observation has not been translationally applied. Using a neonatal mouse model, we tested the hypothesis that passive transfer of HSV-specific human monoclonal antibodies (mAbs) can prevent mortality and morbidity associated with nHSV. The mAbs were expressed in vivo by vectored immunoprophylaxis, or administered in vivo following recombinant expression in vitro. Through these maternally-derived routes or through direct administration to pups, diverse mAbs to HSV glycoprotein D protected against neonatal HSV-1 and HSV-2 infection. Using in vivo bioluminescent imaging, both pre- and post-exposure mAb treatment significantly reduced viral load. Administration of mAb also reduced nHSV-induced behavioral morbidity, as measured by anxiety-like behavior. Together these studies support the notion that HSV-specific mAb-based therapies may prevent or improve HSV infection outcomes in neonates.


2022 ◽  
Vol 12 ◽  
Author(s):  
Xiaowei Song ◽  
Yiliang Wang ◽  
Feng Li ◽  
Wenyan Cao ◽  
Qiongzhen Zeng ◽  
...  

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.


Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 118
Author(s):  
Bangxing Hong ◽  
Upasana Sahu ◽  
Matthew P. Mullarkey ◽  
Balveen Kaur

Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for an oHSV for melanoma, but barriers to this promising therapy still exist that limit efficacy. The process of infection, replication and transmission of oHSV in solid tumors is key to obtaining a good lytic destruction of infected cancer cells to kill tumor cells and release tumor antigens that can prime anti-tumor efficacy. Intracellular tumor cell signaling and tumor stromal cells present multiple barriers that resist oHSV activity. Here, we provide a review focused on oncolytic HSV and the essential viral genes that allow for virus replication and spread in order to gain insight into how manipulation of these pathways can be exploited to potentiate oHSV infection and replication among tumor cells.


2022 ◽  
Vol 0 ◽  
pp. 1-6
Author(s):  
Bini Chandran

Immunotherapy has revolutionized the treatment of extensive and resistant warts. Promising results have extended the role of immunotherapy to other infections such as extensive molluscum contagiosum, recurrent herpes simplex infections, and cutaneous leishmaniasis, which are resistant to standard treatment. This review focuses on topical and intralesional immunotherapy in the management of cutaneous infections.


Author(s):  
Larissa Henze ◽  
Christoph Buhl ◽  
Michael Sandherr ◽  
Oliver A. Cornely ◽  
Werner J. Heinz ◽  
...  

Abstract Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 “Antiviral prophylaxis in patients with solid tumours and haematological malignancies” focusing on herpes simplex virus and varicella zoster virus.


2022 ◽  
Vol 11 (1) ◽  
pp. e25611124670
Author(s):  
Mariana Queiroz Borges ◽  
Daniel Mansur Caldeira ◽  
Ellen Camila Rodrigues ◽  
Zeno Augusto de Sousa Neto ◽  
Mariana Resende Guedes ◽  
...  
Keyword(s):  

O presente estudo tem como objetivo relatar um caso de uma mulher com Síndrome de Ramsay Hunt (SRH). Paciente do gênero feminino, 39 anos, apresentou lesão vascular em pavilhão auditivo externo direito, paralisia facial periférica ipsilateral, posteriormente apresentou perda auditiva parcial em audiometria, apresentando um caso quadro clássico de SRH. Dentre os exames laboratoriais apresentou-se sorologia reagente para Herpes Simplex tipo I e II, IgG reagente e Varícela Zoster, IgM e IgG reagentes. O tratamento utilizado foi aciclovir, tenofovir e predinisona, o que levou a uma melhora parcial da paralisia facial periférica associado ao desaparecimento das lesões. O quadro apresentado demonstra a importância de um diagnóstico precoce e o tratamento feito no período correto é imprescindível para um bom prognóstico, evitando a possível presença de sequelas nervosas motoras mutiladoras.


2022 ◽  
Vol 18 (1) ◽  
pp. e1010225
Author(s):  
Tomasz H. Benedyk ◽  
Julia Muenzner ◽  
Viv Connor ◽  
Yue Han ◽  
Katherine Brown ◽  
...  

2022 ◽  
Author(s):  
Lbachir BenMohamed ◽  
Arif A. Khan ◽  
Ruchi Srivastava ◽  
Hawa Vahed

Herpes simplex virus (HSV)-specific CD8+ T cells protect mice from herpes infection and disease. However, the phenotype and function of HSV-specific CD8+ T cells that play a key role in the "natural" protection seen in HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. We previously reported that symptomatic (SYMP) patients (who have frequent bouts of recurrent herpes disease) had more less-differentiated and dysfunctional HSV-specific CD8+ T cells. In contrast, healthy ASYMP individuals maintained a significantly higher proportion of differentiated polyfunctional CD8+ T cells. Here we report that, HSV-specific CD8+ T cells from SYMP patients, but not from ASYMP individuals, have phenotypic and functional characteristics of cellular senescence, including: (i) high frequency of senescent (CD57+) and exhausted (PD-1+) CD8+ T cells; (ii) late terminally differentiated (KLRG1+), non-proliferating CD8+ T cells; (iii) HSV-specific CD8+ T cells were declined overtime and were not maintained homeostatistically (CD127+CD8+ T cells); (iv) loss of co-stimulatory molecule (CD28)on HSV-specific CD8+ T cells; (v) decreased production of effector molecules (granzyme B and perforin) by HSV-specific CD8+ T cells. Our findings provide insights into the role of senescence in HSV-specific CD8+ T cells in susceptibility to recurrent herpes and have implications for T-cell-based immunotherapeutic strategies against recurrent herpes in humans.


2022 ◽  
Author(s):  
Ruchi Srivastava ◽  
Anshu Agrawal ◽  
Hawa Vahed ◽  
Lbachir BenMohamed

Immune function declines with age, leading to an increased vulnerability to respiratory viral infections. The mechanisms by which aging negatively impacts the innate and adaptive immune system leading to enhanced susceptibility to infections remain to be fully elucidated. In the present study, we used a mouse model of intranasal infection with herpes simplex virus type 1 (HSV-1), a virus that can enter the lungs through the nasal route causing pneumonia, a serious health concern in the elderly. Following intranasal inoculation of young (6 weeks), adult (36 weeks), and aged (68 weeks) with HSV-1 (KOS strain) we: (i) compared the local and systemic innate and adaptive immune response to infection; and (ii) correlated the level and type of immune response to protection against HSV-1 infection. Compared to young and adult mice, aged mice displayed: (i) increased basal level activation of epithelial cells with a decreased expression of TLR3; (ii) increased activation of dendritic cells with increased expression of MHC-1, MHC-II and CD80/86; and (iii) decreased production of type-I interferons upon stimulation; (iv) a delay in cytokines and chemokines production in the lungs; and (v) an impairment in function (CD107 and IFN-g production) of HSV-specific CD8+ T cells. These impairment in innate and adaptive immune responses in aged mice following intranasal HSV-1 inoculation was associated with symptomatic herpes infection. The findings suggest an age-related impairment of both innate and adaptive immune responses which may exacerbate herpes infection and disease in the elderly.


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