Cell Entry Mechanisms of HSV: What we have Learned in Recent Years

Agelidis, Alex; Shukla, Deepak

doi:10.2217/fvl.15.85

Cited by 158 publications

(171 citation statements)

References 77 publications

(95 reference statements)

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“…Herpesviruses are among the most prevalent human infections worldwide, with an estimated 90 percent of individuals worldwide infected with HSV-1 or -2 (Farooq and Shukla, 2012). HSV-1, a prototypic DNA virus, enters cells via multiple well-characterized receptors (Agelidis and Shukla, 2015), and is known to cause distressing infection of the human cornea, with HSV keratitis as the leading cause of infectious blindness in developed nations (Farooq and Shukla, 2012). Current therapies, including acyclovir and its analogs, are limited by their inability to prevent permanent establishment of viral latency and reactivation of clinical disease later in life (Remeijer et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Viral Activation of Heparanase Drives Pathogenesis of Herpes Simplex Virus-1

et al. 2017

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Summary Herpes simplex virus type-1 (HSV-1) causes lifelong recurrent pathologies without a cure. How infection by HSV-1 triggers disease processes, especially in the immune-privileged avascular human cornea, remains a major unresolved puzzle. It has been speculated that a cornea-resident molecule must tip the balance in favor of pro-inflammatory and pro-angiogenic conditions observed with herpetic as well as non-herpetic ailments of the cornea. Here, we demonstrate that heparanase (HPSE), a host enzyme, is the molecular trigger for multiple pathologies associated with HSV-1 infection. In human corneal epithelial cells, HSV-1 infection upregulates HPSE in a manner dependent on HSV-1 infected cell protein 34.5. HPSE then relocates to the nucleus to regulate cytokine production, inhibits wound closure, enhances viral spread, and thus generates a toxic local environment. Overall, our findings implicate activated HPSE as a driver of viral pathogenesis, and call for further attention to this host protein in infection and other inflammatory disorders.

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Section: Introductionmentioning

confidence: 99%

Viral Activation of Heparanase Drives Pathogenesis of Herpes Simplex Virus-1

et al. 2017

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“…Following infection of sensory neurons, HSV-1 can establish latency and later undergo reactivation in response to various factors, including stress, cold temperature, and skin trauma, resulting in the development of cold sores (Antoine et al, 2013). Viral infection depends on several critical steps including attachment to specific receptors on the host cell membrane and entry and replication of viral genes (Agelidis et al, 2015). HSV-1 entry can occur either by direct fusion of the viral envelope with the host cell membrane or by an endocytic mechanism.…”

Section: Introductionmentioning

confidence: 99%

Regulation of T-type Ca2+ channel expression by herpes simplex virus-1 infection in sensory-like ND7 cells

2017

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Infection of sensory neurons by herpes simplex virus (HSV)-1 disrupts electrical excitability, altering pain sensory transmission. Because of their low threshold for activation, functional expression of T-type Ca2+ channels regulates various cell functions, including neuronal excitability and neuronal communication. In this study, we have tested the effect of HSV-1 infection on the functional expression of T-type Ca2+ channels in differentiated ND7-23 sensory-like neurons. Voltage-gated Ca2+ currents were measured using whole cell patch clamp recordings in differentiated ND7-23 neurons under various culture conditions. Differentiation of ND7-23 cells evokes a significant increase in T-type Ca2+ current densities. Increased T-type Ca2+ channel expression promotes the morphological differentiation of ND7-23 cells and triggers a rebound depolarization. HSV-1 infection of differentiated ND7-23 cells causes a significant loss of T-type Ca2+ channels from the membrane. HSV-1 evoked reduction in the functional expression of T-type Ca2+ channels is mediated by several factors, including decreased expression of Cav3.2 T-type Ca2+ channel subunits and disruption of endocytic transport. Decreased functional expression of T-type Ca2+ channels by HSV-1 infection requires protein synthesis and viral replication, but occurs independently of Egr-1 expression. These findings suggest that infection of neuron-like cells by HSV-1 causes a significant disruption in the expression of T-type Ca2+ channels, which can results in morphological and functional changes in electrical excitability.

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“…Tegument proteins participate in a range of viral functions from viral assembly to host cell entry . Complex formation between HSV‐1 glycoproteins and cell receptors initiates the fusion between the host cell and viral membranes, leading to viral capsid uptake …”

Section: Virus Inactivation With Argininementioning

confidence: 99%

Arginine‐enveloped virus inactivation and potential mechanisms

Meingast

Heldt

2019

Biotechnology Progress

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Arginine synergistically inactivates enveloped viruses at a pH or temperature that does little harm to proteins, making it a desired process for therapeutic protein manufacturing. However, the mechanisms and optimal conditions for inactivation are not fully understood, and therefore, arginine viral inactivation is not used industrially. Optimal solution conditions for arginine viral inactivation found in the literature are high arginine concentrations (0.7–1 M), a time of 60 min, and a synergistic factor of high temperature (≥40°C), low pH (≤pH 4), or Tris buffer (5 mM). However, at optimal conditions full inactivation does not occur over all enveloped viruses. Enveloped viruses that are resistant to arginine often have increased protein stability or membrane stabilizing matrix proteins. Since arginine can interact with both proteins and lipids, interaction with either entity may be key to understanding the inactivation mechanism. Here, we propose three hypotheses for the mechanisms of arginine induced inactivation. Hypothesis 1 describes arginine‐induced viral inactivation through inhibition of vital protein function. Hypothesis 2 describes how arginine destabilizes the viral membrane. Hypothesis 3 describes arginine forming pores in the virus membrane, accompanied by further viral damage from the synergistic factor. Once the mechanisms of arginine viral inactivation are understood, further enhancement by the addition of functional groups, charges, or additives may allow the inactivation of all enveloped viruses in mild conditions.

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Cell Entry Mechanisms of HSV: What we have Learned in Recent Years

Cited by 158 publications

References 77 publications

Viral Activation of Heparanase Drives Pathogenesis of Herpes Simplex Virus-1

Viral Activation of Heparanase Drives Pathogenesis of Herpes Simplex Virus-1

Regulation of T-type Ca2+ channel expression by herpes simplex virus-1 infection in sensory-like ND7 cells

Arginine‐enveloped virus inactivation and potential mechanisms

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