Viperin has species-specific roles in response to herpes simplex virus infection

Tseng, Yeu-Yang; Gowripalan, Anjali; Croft, Sarah; Smith, Stewart A.; Helbig, Karla J.; Man, Si Ming; Tscharke, David C.

doi:10.1099/jgv.0.001638

Cited by 6 publications

(3 citation statements)

References 50 publications

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“…Such results are consistent with the findings showing IFN-β expression is elevated in the cornea of HSV-1-infected C3KO mice at this time point as well. Other anti-viral pathways may also be impacted by the loss of C3 including interferon-induced transmembrane protein 1 (IFITM1), IFN-stimulated gene 15 (ISG15), and viperin, all of which possess potent action against HSV-1 infection [63][64][65]. Finally, the loss of C3 in the cornea and its impact on HSV-1 replication is limited since viral titers are similar to WT cornea samples by day three PI [38].…”

Section: Discussionmentioning

confidence: 99%

Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice

Carr,

Filiberti,

Gmyrek

2024

Pathogens

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The complement system (CS) contributes to the initial containment of viral and bacterial pathogens and clearance of dying cells in circulation. We previously reported mice deficient in complement component 3 (C3KO mice) were more sensitive than wild-type (WT) mice to ocular HSV-1 infection, as measured by a reduction in cumulative survival and elevated viral titers in the nervous system but not the cornea between days three and seven post infection (pi). The present study was undertaken to determine if complement deficiency impacted virus replication and associated changes in inflammation at earlier time points in the cornea. C3KO mice were found to possess significantly (p < 0.05) less infectious virus in the cornea at 24 h pi that corresponded with a decrease in HSV-1 lytic gene expression at 12 and 24 h pi compared to WT animals. Flow cytometry acquisition found no differences in the myeloid cell populations residing in the cornea including total macrophage and neutrophil populations at 24 h pi with minimal infiltrating cell populations detected at the 12 h pi time point. Analysis of cytokine and chemokine content in the cornea measured at 12 and 24 h pi revealed that only CCL3 (MIP-1α) was found to be different between WT and C3KO mice with >2-fold increased levels (p < 0.05, ANOVA and Tukey’s post hoc t-test) in the cornea of WT mice at 12 h pi. C3KO mouse resistance to HSV-1 infection at the early time points correlated with a significant increase in type I interferon (IFN) gene expression including IFN-α1 and IFN-β and downstream effector genes including tetherin and RNase L (p < 0.05, Mann–Whitney rank order test). These results suggest early activation of the CS interferes with the induction of the type I IFN response and leads to a transient increase in virus replication following corneal HSV-1 infection.

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Section: Discussionmentioning

confidence: 99%

Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice

Carr,

Filiberti,

Gmyrek

2024

Pathogens

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“…Viperin inhibits the replication of numerous RNA and DNA viruses [ 218 , 219 ]. Recent studies indicate that HSV-1 proteins such as UL41 or virion host shutoff (vhs) can counteract viperin’s antiviral activity to promote HSV-1 replication [ 219 , 220 , 221 ]. HSV-1 vhs, an endoribonuclease, degrades viperin mRNA accumulation and inhibits viperin’s antiviral activity [ 219 ].…”

Section: Anti-hsv-1 Isgsmentioning

confidence: 99%

“…Conversely, HSV-1 has evolved strategies to neutralize ISG-mediated antiviral effector mechanisms. For example, vhs, by its endoribonuclease activity, targets viperin mRNA and thus reduces viperin levels, inhibiting HSV-1 replication [ 219 , 220 ]. vhs also targets tetherin mRNA and protein, thus promoting HSV-1 replication, dissemination, and infection of new cells [ 224 ].…”

Section: Hsv-1 Evasion Strategies To Control Innate Ifn Responsesmentioning

confidence: 99%

Role of Innate Interferon Responses at the Ocular Surface in Herpes Simplex Virus-1-Induced Herpetic Stromal Keratitis

et al. 2023

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Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that primarily infects epithelial cells of the orofacial mucosa. After initial lytic replication, HSV-1 enters sensory neurons and undergoes lifelong latency in the trigeminal ganglion (TG). Reactivation from latency occurs throughout the host’s life and is more common in people with a compromised immune system. HSV-1 causes various diseases depending on the site of lytic HSV-1 replication. These include herpes labialis, herpetic stromal keratitis (HSK), meningitis, and herpes simplex encephalitis (HSE). HSK is an immunopathological condition and is usually the consequence of HSV-1 reactivation, anterograde transport to the corneal surface, lytic replication in the epithelial cells, and activation of the host’s innate and adaptive immune responses in the cornea. HSV-1 is recognized by cell surface, endosomal, and cytoplasmic pattern recognition receptors (PRRs) and activates innate immune responses that include interferons (IFNs), chemokine and cytokine production, as well as the recruitment of inflammatory cells to the site of replication. In the cornea, HSV-1 replication promotes type I (IFN-α/β) and type III (IFN-λ) IFN production. This review summarizes our current understanding of HSV-1 recognition by PRRs and innate IFN-mediated antiviral immunity during HSV-1 infection of the cornea. We also discuss the immunopathogenesis of HSK, current HSK therapeutics and challenges, proposed experimental approaches, and benefits of promoting local IFN-λ responses.

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Bovine cyclic GMP-AMP synthase recognizes exogenous double-stranded DNA and activates the STING-depended interferon β production pathway

Dai¹,

Wang²,

Fan³

et al. 2023

Developmental & Comparative Immunology

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Viperin has species-specific roles in response to herpes simplex virus infection

Cited by 6 publications

References 50 publications

Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice

Complement Suppresses the Initial Type 1 Interferon Response to Ocular Herpes Simplex Virus Type 1 Infection in Mice

Role of Innate Interferon Responses at the Ocular Surface in Herpes Simplex Virus-1-Induced Herpetic Stromal Keratitis

Bovine cyclic GMP-AMP synthase recognizes exogenous double-stranded DNA and activates the STING-depended interferon β production pathway

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