更新于：2024-11-01

HSV Gc

更新于：2024-11-01

基本信息

别名-

简介-

关联

靶点

HSV Gc x HSV gD x HSV gE

作用机制

HSV Gc 调节剂 [+2]

在研机构

University of Pennsylvania

原研机构-

在研适应症

生殖器疱疹

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 HSV Gc 相关的临床结果

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100 项与 HSV Gc 相关的转化医学

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0 项与 HSV Gc 相关的专利（医药）

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273

项与 HSV Gc 相关的文献（医药）

2024-08-01·Virus Research

Convalescent human plasma candidate reference materials protect against Crimean-Congo haemorrhagic fever virus (CCHFV) challenge in an A129 mouse model

Article

作者: Charlton, Frank W ; Dowall, Stuart ; Duru, Chinwe ; Oz, Murtaza ; Arnold, Ulrike ; Hewson, Roger ; Salguero, Francisco J ; Almond, Neil ; Matejtschuk, Paul ; Mirazimi, Ali ; Hassall, Mark ; Elaldi, Nazif ; Kennedy, Emma ; Bagci, Binnur ; Ezeajughi, Ernest ; Barr, John N ; Fontana, Juan ; Graham, Victoria ; Tasseten, Tuba ; Kempster, Sarah ; Adedeji, Yemisi ; Findlay-Wilson, Stephen

Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is spread by infected ticks or direct contact with blood, tissues and fluids from infected patients or livestock. Infection with CCHFV causes severe haemorrhagic fever in humans which is fatal in up to 83 % of cases. CCHFV is listed as a priority pathogen by the World Health Organization (WHO) and there are currently no widely-approved vaccines. Defining a serological correlate of protection against CCHFV infection would support the development of vaccines by providing a 'target threshold' for pre-clinical and clinical immunogenicity studies to achieve in subjects and potentially obviate the need for in vivo protection studies. We therefore sought to establish titratable protection against CCHFV using pooled human convalescent plasma, in a mouse model. Convalescent plasma collected from seven individuals with a known previous CCHFV virus infection were characterised using binding antibody and neutralisation assays. All plasma recognised nucleoprotein and the Gc glycoprotein, but some had a lower Gn glycoprotein response by ELISA. Pooled plasma and two individual donations from convalescent donors were administered intraperitoneally to A129 mice 24 h prior to intradermal challenge with CCHFV (strain IbAr10200). A partial protective effect was observed with all three convalescent plasmas characterised by longer survival post-challenge and reduced clinical score. These protective responses were titratable. Further characterisation of the serological reactivities within these samples will establish their value as reference materials to support assay harmonisation and accelerate vaccine development for CCHFV.

2024-08-01·Virology

Enhancement of HSV-1 cell-free virion release by the envelope protein gC

Article

作者: Frost, Thomas C ; Salnikov, Mark ; Rice, Stephen A

Glycoprotein C (gC), one of ∼12 HSV-1 envelope glycoproteins, carries out several important functions during infection, including the enhancement of virion attachment by binding to host cell heparan sulfate proteoglycans (HSPG). Here we report that gC can also enhance the release of cell-free progeny virions at the end of the infectious cycle. This activity was observed in multiple cellular contexts including Vero cells and immortalized human keratinocytes. In the absence of gC, progeny virions bound more tightly to infected cells, suggesting that gC promotes the detachment of virions from the infected cell surface. Given this finding, we analyzed the biochemical interactions that tether progeny virions to cells and report evidence for two distinct modes of binding. One is consistent with a direct interaction between gC and HSPG, whereas the other is gC-independent and likely does not involve HSPG. Together, our results i) identify a novel function for a long-studied HSV-1 glycoprotein, and ii) demonstrate that the extracellular release of HSV-1 virions is a dynamic process involving multiple viral and host components.

2023-08-31·Journal of virology

The La Crosse virus class II fusion glycoprotein ij loop contributes to infectivity and replication in vitro and in vivo.

Article

作者: Stapleford, Kenneth A ; Thannickal, Sara A ; Spector, Sophie N

Arthropod-borne viruses (arboviruses) are an emerging and evolving global public health threat, with limited antiviral treatments or vaccines available. La Crosse virus (LACV) from the Bunyavirales order is responsible for pediatric encephalitis cases in the United States, yet little is known about the infectivity of LACV. Given the structural similarities between class II fusion glycoproteins of LACV and chikungunya virus (CHIKV), an alphavirus from the Togaviridae family, we hypothesized that LACV would share similar entry mechanisms with CHIKV. To test this hypothesis, we performed cholesterol-depletion and repletion assays and used cholesterol-modulating compounds to study LACV entry and replication. We found that LACV entry was cholesterol dependent, while replication was less affected by cholesterol manipulation. In addition, we generated single-point mutants in the LACV Gc ij loop that corresponded to known CHIKV residues important for virus entry. We found that a conserved histidine and alanine residue in the Gc ij loop impaired virus infectivity and attenuated LACV replication in vitro and in vivo. Finally, we took an evolution-based approach to explore how the LACV glycoprotein evolves in mosquitoes and mice. We found multiple variants that cluster in the Gc glycoprotein head domain, providing evidence for the Gc glycoprotein as a contributor to LACV adaptation. Together, these results begin to characterize the mechanisms of LACV infectivity and how the LACV glycoprotein contributes to replication and pathogenesis. IMPORTANCE Vector-borne viruses are significant health threats that lead to devastating disease worldwide. The emergence of arboviruses, in addition to the lack of effective antivirals or vaccines, highlights the need to study how arboviruses replicate at the molecular level. One potential antiviral target is the class II fusion glycoprotein. Alphaviruses, flaviviruses, and bunyaviruses encode a class II fusion glycoprotein that contains strong structural similarities at the tip of domain II. Here, we show that the bunyavirus La Crosse virus uses a cholesterol-dependent entry pathway similar to the alphavirus chikungunya virus, and residues in the ij loop are important for virus infectivity in vitro and replication in mice. These studies show that genetically diverse viruses may use similar pathways through conserved structure domains, suggesting that these viruses may be targets for broad-spectrum antivirals in multiple arboviral families.