Colonization of peripheral ganglia by herpes simplex virus type 1 and 2

Kropp, Kai A.; Sun, Guorong; Viejo‐Borbolla, Abel

doi:10.1016/j.coviro.2023.101333

Cited by 5 publications

(1 citation statement)

References 75 publications

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“…Initial HSV infection occurs in epithelial cells of the orolabial and genital mucosa as well as in the skin and cornea ( 4 ). Following replication in epithelial cells, HSV-1 and HSV-2 reach and enter neurites to colonize neurons and establish lifelong latency in the ganglia of the peripheral nervous system (PNS) ( 5 – 8 ). Latent HSV-1 and HSV-2 reactivate frequently, producing infectious viruses that travel in an anterograde manner within neurites toward peripheral tissues, where they cause recurrent diseases and spread to other individuals ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Herpes simplex virus type 1 modifies the protein composition of extracellular vesicles to promote neurite outgrowth and neuroinfection

Sun,

Kropp,

Kirchner

et al. 2024

mBio

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The highly prevalent herpes simplex virus type 1 (HSV-1) causes a range of diseases, including cold sores, blinding keratitis, and life-threatening encephalitis. HSV-1 initially replicates in epithelial cells, enters the peripheral nervous system via neurites, and establishes lifelong infection in the neuronal cell bodies. Neurites are highly dynamic structures that grow or retract in response to attractive or repulsive cues, respectively. Here, we show that infection with HSV-1, but not with a mutant virus lacking glycoprotein G (gG), reduced the repulsive effect of epithelial cells on neurite outgrowth and facilitated HSV-1 invasion of neurons. HSV-1 gG was required and sufficient to induce neurite outgrowth by modifying the protein composition of extracellular vesicles, increasing the amount of neurotrophic and neuroprotective proteins, including galectin-1. Antibodies directed against galectin-1 neutralized the capacity of extracellular vesicles released from HSV-1-infected cells to promote neurite outgrowth. Our study provides new insights into the neurotropism of HSV-1 and identifies a viral protein that modifies the protein composition of extracellular vesicles to stimulate neurite outgrowth and invasion of the nervous system. IMPORTANCE Herpes simplex virus type 1 (HSV-1) must infect neurites (or nerve endings) to establish a chronic infection in neurons. Neurites are highly dynamic structures that retract or grow in the presence of repulsive or attractive proteins. Some of these proteins are released by epithelial cells in extracellular vesicles and act upon interaction with their receptor present on neurites. We show here that HSV-1 infection of epithelial cells modulated their effect on neurites, increasing neurite growth. Mechanistically, HSV-1 glycoprotein G (gG) modifies the protein composition of extracellular vesicles released by epithelial cells, increasing the amount of attractive proteins that enhance neurite outgrowth and facilitate neuronal infection. These results could inform of therapeutic strategies to block HSV-1 induction of neurite outgrowth and, thereby, neuronal infection.

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Section: Introductionmentioning

confidence: 99%

Herpes simplex virus type 1 modifies the protein composition of extracellular vesicles to promote neurite outgrowth and neuroinfection

Sun,

Kropp,

Kirchner

et al. 2024

mBio

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Immune Evasion Mechanism of Neurotropic Viruses

Yan,

Sun,

Guo

et al. 2024

Reviews in Medical Virology

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The persistent challenge posed by viruses that infect the central nervous system lies in their sophisticated ability to evade the host immune system. This review explores into the complex mechanisms of immune evasion employed by these neurotropic viruses, focussing on their modulation of host immune responses, evasion of adaptive immunity, and the cellular and molecular strategies that enable their persistence. Key areas explored include viral latency and reactivation, the inhibition of apoptosis, and antigenic variation, with a detailed examination of viral proteins and their interactions with host cellular processes.

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CRISPR/Cas9 Eye Drop HSV-1 Treatment Reduces Brain Viral Load: A Novel Application to Prevent Neuronal Damage

de Sousa,

Garcia,

Lemos

et al. 2024

Pathogens

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Herpes simplex virus-1 (HSV-1) can invade the central nervous system (CNS). However, antiviral drugs used to treat HSV-1 have significant toxicity and resistance. An alternative approach involves the use of the CRISPR/Cas9 complex as a viral replication inhibitor. Editing the UL39 gene with CRISPR/Cas9 results in >95% inhibition of HSV-1 replication in vitro; however, few studies have investigated alternative therapies in in vivo models. This study aimed to investigate the efficacy of CRISPR/Cas9 targeting the UL39 region, which was administered via the ocular route, to reduce the HSV-1 viral count in the CNS of BALB/c mice. Mice were inoculated with HSV-1 and treated using CRISPR/Cas9. The kinetics of CNS infection were assessed, and the effects of CRISPR/Cas9 were compared with those of topical acyclovir treatments. The brain viral load was analyzed, and histopathology and immunofluorescence of the nervous tissue were performed. The group treated with CRISPR/Cas9 showed a reduced viral load on the seventh day post-infection, and no brain inflammation or chromatin compaction was observed in animals that received CRISPR/Cas9 therapy. These findings suggest that CRISPR/Cas9 anti-UL39 therapy can reduce the HSV-1 viral load in brain tissue. Therefore, investigating viral detection and evaluating antiviral treatments in the brain is essential.

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Colonization of peripheral ganglia by herpes simplex virus type 1 and 2

Cited by 5 publications

References 75 publications

Herpes simplex virus type 1 modifies the protein composition of extracellular vesicles to promote neurite outgrowth and neuroinfection

Herpes simplex virus type 1 modifies the protein composition of extracellular vesicles to promote neurite outgrowth and neuroinfection

Immune Evasion Mechanism of Neurotropic Viruses

CRISPR/Cas9 Eye Drop HSV-1 Treatment Reduces Brain Viral Load: A Novel Application to Prevent Neuronal Damage

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