Conformational Changes in Herpes Simplex Virus Glycoprotein C

Gianopulos, Katrina A.; Sari, Tri Komala; Weed, Darin J.; Pritchard, Suzanne M.; Nicola, Anthony V.

doi:10.1128/jvi.00163-22

Cited by 8 publications

(6 citation statements)

References 64 publications

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“…gC is not strictly required for HSV entry, but mediates cell attachment [ 31 ] and influences gB conformational changes during endosomal entry [ 32 ]. gC itself also undergoes pH-triggered conformational changes [ 33 ]. The ANG UL45 gene was sequenced as a control and, interestingly, was identical to other wild type strains ( Table 1 ).…”

Section: Resultsmentioning

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: Resultsmentioning

confidence: 99%

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

Gianopulos,

Makio,

Pritchard

et al. 2024

Viruses

Self Cite

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show abstract

“…gC is not strictly required for HSV entry, but mediates cell attachment (36) and influences gB conformational changes during endosomal entry (37). gC itself also undergoes pH-triggered conformational changes (38). The ANG UL45 gene was sequenced as a control and, interestingly, was identical to wild type (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Membrane fusion activity of herpes simplex virus 1 glycoproteins from a hyperfusogenic virus

Gianopulos,

Makio,

Pritchard

et al. 2023

Preprint

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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 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. 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 gD and gH/gL, increased membrane fusion, suggesting that ANG gB has hyperfusogenic cell-cell fusion activity. Replacing the wild type gD, gH, or gL with the corresponding ANG alleles did not enhance cell-cell fusion. Wild type gC is proposed to facilitate fusion and entry into epithelial cells by optimizing conformational changes in the fusion protein gB. ANG gC substitution or addition also had no effect on 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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“…gC contributes to entry by binding to cell surface glycosaminoglycans ( 48 ). Recent work has shown that gC can regulate entry via a low-pH pathway and impact gB conformational changes ( 49 , 50 ). Whether these gC and gH mutations contributed to the enhanced entry observed in these passaged viruses may be the subject of future work.…”

Section: Discussionmentioning

confidence: 99%

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

Fan

Hippler

Yang

et al. 2023

mBio

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Enveloped viruses enter cells by fusing their envelope with the host cell membrane. Herpes simplex virus 1 (HSV-1) entry requires the coordinated interaction of several viral glycoproteins, including gH/gL and gB. gH/gL and gB are essential for virus replication and both proteins are targets of neutralizing antibodies. gB fuses the membranes after being activated by gH/gL, but the details of how gH/gL activates gB are not known.

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Conformational Changes in Herpes Simplex Virus Glycoprotein C

Abstract: Herpesviruses are ubiquitous pathogens that cause lifelong latent infections and are characterized by multiple entry pathways. The HSV envelope gC regulates HSV entry by a low-pH entry route.

Cited by 8 publications

References 64 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

Membrane fusion activity of herpes simplex virus 1 glycoproteins from a hyperfusogenic virus

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

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