Multiple Sites on Glycoprotein H (gH) Functionally Interact with the gB Fusion Protein to Promote Fusion during Herpes Simplex Virus (HSV) Entry

Fan, Qing; Hippler, Daniel P; Yang, Yueqi; Longnecker, Richard; Connolly, Sarah A.

doi:10.1128/mbio.03368-22

Cited by 5 publications

(3 citation statements)

References 59 publications

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“…Endosomal low pH has been proposed to induce fusion-activating changes in gB in a cell-specific manner [ 59 , 60 ]. The gH cytoplasmic tail is thought to function as a wedge that is inserted into a pocket on the gB cytoplasmic tail prior to fusion [ 43 , 61 ]. The fusion reaction culminates in gB refolding, and the merger of viral and host membranes forming a fusion pore.…”

Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus 1 Glycoprotein B from a Hyperfusogenic Virus Mediates Enhanced Cell–Cell Fusion

Gianopulos,

Makio,

Pritchard

et al. 2024

Viruses

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Herpes simplex virus 1 (HSV-1) causes significant morbidity and death in humans worldwide. Herpes simplex virus 1 has a complex fusion mechanism that is incompletely understood. The HSV-1 strain ANG has notable fusion and entry activities that distinguish it from wild type. HSV-1 ANG virions fused with the Vero cell surface at 4 °C and also entered cells more efficiently at 15 °C, relative to wild type HSV-1 strain KOS virions, consistent with a hyperfusogenic phenotype. Understanding the molecular basis for the unique entry and fusion activities of HSV-1 strain ANG will help decipher the HSV fusion reaction and entry process. Sequencing of HSV-1 ANG genes revealed multiple changes in gB, gC, gD, gH, and gL proteins relative to wild type HSV-1 strains. The ANG UL45 gene sequence, which codes for a non-essential envelope protein, was identical to wild type KOS. HSV-1 ANG gB, gD, and gH/gL were necessary and sufficient to mediate cell–cell fusion in a virus-free reporter assay. ANG gB, when expressed with wild type KOS gD and gH/gL, increased membrane fusion, suggesting that ANG gB has hyperfusogenic cell–cell fusion activity. Replacing the KOS gD, gH, or gL with the corresponding ANG alleles did not enhance cell–cell fusion. The novel mutations in the ANG fusion and entry glycoproteins provide a platform for dissecting the cascade of interactions that culminate in HSV fusion and entry.

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Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus 1 Glycoprotein B from a Hyperfusogenic Virus Mediates Enhanced Cell–Cell Fusion

Gianopulos,

Makio,

Pritchard

et al. 2024

Viruses

View full text Add to dashboard Cite

show abstract

“…When viruses invade cells, glycoproteins gB, gD, gH and gL form complexes to modify cell membrane proteins and induce the formation of syncytia, the classic manifestation of herpesvirus infection ( Atanasiu et al, 2010 , 2016 ; Böhm et al, 2016 ; Pataki et al, 2022a ). As a fusion protein, the gB protein promotes the formation of syncytia, while UL24, gK and UL20 inhibit cell fusion ( Atanasiu et al, 2010 , 2013 ; Fan et al, 2023 ). UL24 can change the localization of gB, gD and F-actin to inhibit cell fusion and cause syncytial plaques in infected cells ( Avitabile et al, 2004 ; Bertrand et al, 2010 ).…”

Section: Ul24 Inhibits Cell Fusionmentioning

confidence: 99%

Mechanism of herpesvirus UL24 protein regulating viral immune escape and virulence

Ruan,

Wang,

Cheng

et al. 2023

Front. Microbiol.

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Herpesviruses have evolved a series of abilities involved in the process of host infection that are conducive to virus survival and adaptation to the host, such as immune escape, latent infection, and induction of programmed cell death for sustainable infection. The herpesvirus gene UL24 encodes a highly conserved core protein that plays an important role in effective viral infection. The UL24 protein can inhibit the innate immune response of the host by acting on multiple immune signaling pathways during virus infection, and it also plays a key role in the proliferation and pathogenicity of the virus in the later stage of infection. This article reviews the mechanism by which the UL24 protein mediates herpesvirus immune escape and its effects on viral proliferation and virulence by influencing syncytial formation, DNA damage and the cell cycle. Reviewing these studies will enhance our understanding of the pathogenesis of herpesvirus infection and provide evidence for new strategies to combat against viral infection.

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“…gB, a member of class III fusogen (Heldwein et al, 2006), binds to one of its receptors to initiate membrane fusion. Recently, it was revealed that gB interacts with multiple sites on gH to promote membrane fusion (Fan et al, 2023). There are three types of gB receptors (Table 2), including paired immunoglobulin-like receptor (PILRa), an inhibitory receptor found on macrophages, dendritic cells, and monocytes (Satoh and Arase, 2008), myelin-associated glycoprotein (MAG) which expresses on glial cells (Suenaga et al, 2010), and non-muscle myosin heavy chain-IIA (NMHC-IIA) on human tissue (Agelidis and Shukla, 2015).…”

Section: Hsv Entrymentioning

confidence: 99%

Impact of actin polymerization and filopodia formation on herpes simplex virus entry in epithelial, neuronal, and T lymphocyte cells

Sasivimolrattana,

Bhattarakosol

2023

Front. Cell. Infect. Microbiol.

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Herpes simplex virus type 1 (HSV-1) has been known as a common viral pathogen that can infect several parts of the body, leading to various clinical manifestations. According to this diverse manifestation, HSV-1 infection in many cell types was demonstrated. Besides the HSV-1 cell tropism, e.g., fibroblast, epithelial, mucosal cells, and neurons, HSV-1 infections can occur in human T lymphocyte cells, especially in activated T cells. In addition, several studies found that actin polymerization and filopodia formation support HSV-1 infection in diverse cell types. Hence, the goal of this review is to explore the mechanism of HSV-1 infection in various types of cells involving filopodia formation and highlight potential future directions for HSV-1 entry-related research. Moreover, this review covers several strategies for possible anti-HSV drugs focused on the entry step, offering insights into potential therapeutic interventions.

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Multiple Sites on Glycoprotein H (gH) Functionally Interact with the gB Fusion Protein to Promote Fusion during Herpes Simplex Virus (HSV) Entry

Cited by 5 publications

References 59 publications

Herpes Simplex Virus 1 Glycoprotein B from a Hyperfusogenic Virus Mediates Enhanced Cell–Cell Fusion

Herpes Simplex Virus 1 Glycoprotein B from a Hyperfusogenic Virus Mediates Enhanced Cell–Cell Fusion

Mechanism of herpesvirus UL24 protein regulating viral immune escape and virulence

Impact of actin polymerization and filopodia formation on herpes simplex virus entry in epithelial, neuronal, and T lymphocyte cells

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