Herpes Simplex Virus Type-1: Replication, Latency, Reactivation and its Antiviral Targets

Mello, Camilly P Pires de; Bloom, David C.; Paixão, Izabel C N P

doi:10.3851/imp3018

Cited by 45 publications

(38 citation statements)

References 127 publications

(166 reference statements)

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“…Herpes simplex virus (HSV), classified as type 1 and 2, is highly prevalent contagious pathogen affecting skin and mucosal tissues of up to 67% of adolescents and adults worldwide [ 1 , 2 ]. HSV-1 infection, which is predominantly spread by oral-to-oral contacts, usually occurs during childhood causing Herpes labialis (with symptoms recognized as “cold sores”), although it may be associated with more serious complications, including ocular herpes or encephalitis [ 3 , 4 ]. Contrarily, HSV-2 is practically entirely sexually transmitted and is therefore most closely related to genital herpes characterized by the presence of painful ulcerative or vesicular lesions [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies

Szymańska

Orłowski

Winnicka

et al. 2018

IJMS

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Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection.

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Section: Introductionmentioning

confidence: 99%

Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies

Szymańska

Orłowski

Winnicka

et al. 2018

IJMS

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“…After acute infection of oral, nasal, or ocular mucosal epithelium, the virus enters the sensory neuron and moves via retrograde transport inside the axon to reach the cell body, which is located within the sensory ganglia, where the virus establishes latency (Perng and Jones, 2010 ; Pires de Mello et al, 2016 ). During latency, viral gene expression ceases except for latency-associated transcripts known as LATs, which facilitate the establishment of latency and inhibit host cell apoptosis (Perng and Jones, 2010 ).…”

Section: Hsv-1 Prevalence Structure and Life Cyclementioning

confidence: 99%

Molecular Mechanisms for Herpes Simplex Virus Type 1 Pathogenesis in Alzheimer’s Disease

Harris

2018

Front. Aging Neurosci.

121

149

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This review focuses on research in the areas of epidemiology, neuropathology, molecular biology and genetics that implicates herpes simplex virus type 1 (HSV-1) as a causative agent in the pathogenesis of sporadic Alzheimer’s disease (AD). Molecular mechanisms whereby HSV-1 induces AD-related pathophysiology and pathology, including neuronal production and accumulation of amyloid beta (Aβ), hyperphosphorylation of tau proteins, dysregulation of calcium homeostasis, and impaired autophagy, are discussed. HSV-1 causes additional AD pathologies through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis. The AD susceptibility genes apolipoprotein E (APOE), phosphatidylinositol binding clathrin assembly protein (PICALM), complement receptor 1 (CR1) and clusterin (CLU) are involved in the HSV lifecycle. Polymorphisms in these genes may affect brain susceptibility to HSV-1 infection. APOE, for example, influences susceptibility to certain viral infections, HSV-1 viral load in the brain, and the innate immune response. The AD susceptibility gene cholesterol 25-hydroxylase (CH25H) is upregulated in the AD brain and is involved in the antiviral immune response. HSV-1 interacts with additional genes to affect cognition-related pathways and key enzymes involved in Aβ production, Aβ clearance, and hyperphosphorylation of tau proteins. Aβ itself functions as an antimicrobial peptide (AMP) against various pathogens including HSV-1. Evidence is presented supporting the hypothesis that Aβ is produced as an AMP in response to HSV-1 and other brain infections, leading to Aβ deposition and plaque formation in AD. Epidemiologic studies associating HSV-1 infection with AD and cognitive impairment are discussed. Studies are reviewed supporting subclinical chronic reactivation of latent HSV-1 in the brain as significant in the pathogenesis of AD. Finally, the rationale for and importance of clinical trials treating HSV-1-infected MCI and AD patients with antiviral medication is discussed.

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“…HSV infection has a latent course, and reactivates in situations of impaired immunity or pathologies of other bodily systems, the nervous system in particular [1,2]. Although the peculiarities and consequences of acute HSV-I infection in the brain are quite well-studied [3,4], little is known about the damage to other organs which are not a source of latent HSV-I infection, the liver in particular. What is more, the literature does not provide any reliable evidence on the poststroke development of herpetic infection.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural changes in murine liver following HSV infection and stroke

Motorna

Рыбалко

Kvitnitskaya-Ryzhova

et al. 2018

Current Issues in Pharmacy and Medical Sciences

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The study of herpetic infection is a topical problem. Although the peculiarities and consequences of acute HSV-I infection in the brain are quite well-studied, little is known about the damage to other organs which are not a source of latent HSV-I infection, the liver in particular. The current study is aimed at determining the ultrastructural changes in murine liver following HSV infection and stroke. Liver samples obtained from four groups of animals were studied: 1) intact mice; 2) mice with stroke; 3) mice infected with HSV-I; 4) mice aflicted with HSV-I and subsequently simulated stroke. The study showed the reproduction of the virus in hepatic endotheliocytes, although no virions were detected in the hepatocytes. Therefore, the described changes were considered the consequences of the infectious process. Pathological changes of hepatocytes consisted of deformation and fragmentation of the nuclei, as well as accumulation of osmiophilic granules, lysosomes and lamellary bodies. Latent HSV-I infection may reactivate in liver after the stroke, potentially causing the complications of the underlying disease.

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Herpes Simplex Virus Type-1: Replication, Latency, Reactivation and its Antiviral Targets

Cited by 45 publications

References 127 publications

Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies

Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies

Molecular Mechanisms for Herpes Simplex Virus Type 1 Pathogenesis in Alzheimer’s Disease

Ultrastructural changes in murine liver following HSV infection and stroke

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