Entry of betaherpesviruses

Nishimura, Mitsuhiro; Mori, Yasuko

doi:10.1016/bs.aivir.2019.05.005

Cited by 19 publications

(13 citation statements)

References 163 publications

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“…In beta-and gammaherpesviruses, gHgL, either alone or in complex with other viral proteins, binds to cellular receptors (Chen et al, 2018;Chen et al, 2019;Chesnokova and Hutt-Fletcher, 2011;Chesnokova et al, 2009;Hahn et al, 2012;Nishimura and Mori, 2019;Santoro et al, 2003;Wang and Shenk, 2005). Although most alphaherpesviruses use gD as a receptor binding protein, gHgL may bind its own cellular ligand(s) as well during entry.…”

Section: Ghgl As a Receptor-binding Proteinmentioning

confidence: 99%

Entry of Alphaherpesviruses

Cairns¹,

Connolly²

2021

Current Issues in Molecular Biology

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Alphaherpesviruses are enveloped viruses that enter cells by fusing the viral membrane with a host cell membrane, either within an endocytic vesicle or at the plasma membrane. This entry event is mediated by a set of essential entry glycoproteins, including glycoprotein D (gD), gHgL, and gB. gHgL and gB are conserved among herpesviruses, but gD is unique to the alphaherpesviruses and is not encoded by all alphaherpesviruses. gD is a receptor-binding protein, the heterodimer gHgL serves as a fusion regulator, and gB is a class III viral fusion protein. Sequential interactions among these glycoproteins are thought to trigger the virus to fuse at the right place and time. Structural studies of these glycoproteins from multiple alphaherpesviruses has enabled the design and interpretation of functional studies. The structures of gD in a receptorbound and in an unliganded form reveal a conformational change in the C terminus of the gD ectodomain upon receptor binding that may serve as a signal for fusion. By mapping neutralizing antibodies to the gHgL structures and constructing interspecies chimeric forms of gHgL, interaction sites for both gD and gB on gHgL have been proposed. A comparison of the postfusion caister.com/cimb 63 Curr. Issues Mol. Biol. Vol. 41 Entry of AlphaherpesvirusesCairns and Connolly structure of gB and an alternative conformation of gB visualized using cryoelectron tomography suggests that gB undergoes substantial refolding to execute membrane fusion. Although these structures have provided excellent insights into the entry mechanism, many questions remain about how these viruses coordinate the interactions and conformational changes required for entry.

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Section: Ghgl As a Receptor-binding Proteinmentioning

confidence: 99%

Entry of Alphaherpesviruses

Cairns¹,

Connolly²

2021

Current Issues in Molecular Biology

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“…Years of research on the host entry mechanism of viruses from the Herpesviridae family has led to the conclusion that, despite the extensive cell tropism that they exhibit, host cell infection takes place through a conserved mechanism [ 4 ]. The entry machinery is formed by a conserved core fusion machinery (formed the heterodimer gH-gL and the fusion protein gB) and by divergent proteins such as gD for HSV-2 or gO for HCMV [ 34 , 35 ]. The latter act as ligands that bind to different host cell receptors, being the first step of the entry process the interaction with distinct classes of HSPGs located on the exterior surface of target cells [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Prevention of Herpesviridae Infections by Cationic PEGylated Carbosilane Dendrimers

et al. 2022

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Infections caused by viruses from the Herpesviridae family produce some of the most prevalent transmitted diseases in the world, constituting a serious global public health issue. Some of the virus properties such as latency and the appearance of resistance to antiviral treatments complicate the development of effective therapies capable of facing the infection. In this context, dendrimers present themselves as promising alternatives to current treatments. In this study, we propose the use of PEGylated cationic carbosilane dendrimers as inhibitors of herpes simplex virus 2 (HSV-2) and human cytomegalovirus (HCMV)infections. Studies of mitochondrial toxicity, membrane integrity, internalization and viral infection inhibition indicated that G2-SN15-PEG, G3-SN31-PEG, G2-SN15-PEG fluorescein isothiocyanate (FITC) labeled and G3-SN31-PEG-FITC dendrimers are valid candidates to target HSV-2 and HCMV infections since they are biocompatible, can be effectively internalized and are able to significantly inhibit both infections. Later studies (including viral inactivation, binding inhibition, heparan sulphate proteoglycans (HSPG)binding and surface plasmon resonance assays) confirmed that inhibition takes place at first infection stages. More precisely, these studies established that their attachment to cell membrane heparan sulphate proteoglycans impede the interaction between viral glycoproteins and these cell receptors, thus preventing infection. Altogether, our research confirmed the high capacity of these PEGylated carbosilane dendrimers to prevent HSV-2 and HCMV infections, making them valid candidates as antiviral agents against Herpesviridae infections.

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“…There are multiple gH complexes, from the newly discovered gH interaction with UL116 [gH (UL75)/UL116] (Caló et al, 2016) to the known gH complexes of gH/gL (UL115)/gO (UL174) or the trimer (Stegmann et al, 2017a) and gH/gL/UL128-131 or the pentamer Nishimura and Mori, 2019). These unique complexes directly affect cell-type-specific entry.…”

Section: Hcmv Receptors and Ligand-induced Signaling Pathway And Cells Hcmv Glycoproteinsmentioning

confidence: 99%

“…To contact a target host cell, the viral ligands in the envelope, gB (UL55), gH (UL75)/gL (UL115)/gO (ULl74), which make up the gH/gL/gO complex or the trimer, and the gH/gL/UL128-131 complex or the pentamer, and gM (UL100)/gN (UL73) interact with cellular receptors that in turn lead to the activation of various signal molecules in the infected host cells (Mach et al, 2005;Shimamura et al, 2006;Shen et al, 2007;Stegmann et al, 2017a;Liu et al, 2018;Gerna et al, 2019;Nishimura and Mori, 2019). There are some receptors that seem to be present on most infected cell types and these include heparan sulfate proteoglycans, cellular integrins (α2β1, α6β1, and αvβ3) (Feire et al, 2004;Wang et al, 2005) and Tolllike receptors (Compton et al, 2003;Boehme et al, 2006), while other receptors such as EGFR (Wang et al, 2003(Wang et al, , 2005, are only found on some cell types and may help dictate tropism.…”

Section: Introductionmentioning

confidence: 99%

“…There are some receptors that seem to be present on most infected cell types and these include heparan sulfate proteoglycans, cellular integrins (α2β1, α6β1, and αvβ3) (Feire et al, 2004;Wang et al, 2005) and Tolllike receptors (Compton et al, 2003;Boehme et al, 2006), while other receptors such as EGFR (Wang et al, 2003(Wang et al, , 2005, are only found on some cell types and may help dictate tropism. Other potential tropism receptors include the Platelet-Derived Growth Factor Receptor [PDGFR (Wu et al, 2017;Wu et al, 2018;Nishimura and Mori, 2019)], Neuropilin-2 [Nrp-2 (Martinez-Martin et al, 2018)], and Olfactory Receptor Family 14 Subfamily I Member 1 [OR14I1 (Xiaofei et al, 2019)]. In general, whether these receptors are specific for a specific cell type or are more conserved across a variety of cell types, they are important for viral attachment, internalization, and fusion and entry into the cytoplasm of the infected cell (Nowlin et al, 1991;Navarro et al, 1993;Boyle and Compton, 1998;Compton, 2000;Isaacson and Compton, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Human Cytomegalovirus Host Interactions: EGFR and Host Cell Signaling Is a Point of Convergence Between Viral Infection and Functional Changes in Infected Cells

et al. 2021

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Viruses have evolved diverse strategies to manipulate cellular signaling pathways in order to promote infection and/or persistence. Human cytomegalovirus (HCMV) possesses a number of unique properties that allow the virus to alter cellular events required for infection of a diverse array of host cell types and long-term persistence. Of specific importance is infection of bone marrow derived and myeloid lineage cells, such as peripheral blood monocytes and CD34+ hematopoietic progenitor cells (HPCs) because of their essential role in dissemination of the virus and for the establishment of latency. Viral induced signaling through the Epidermal Growth Factor Receptor (EGFR) and other receptors such as integrins are key control points for viral-induced cellular changes and productive and latent infection in host organ systems. This review will explore the current understanding of HCMV strategies utilized to hijack cellular signaling pathways, such as EGFR, to promote the wide-spread dissemination and the classic life-long herpesvirus persistence.

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Entry of betaherpesviruses

Cited by 19 publications

References 163 publications

Entry of Alphaherpesviruses

Entry of Alphaherpesviruses

Prevention of Herpesviridae Infections by Cationic PEGylated Carbosilane Dendrimers

Human Cytomegalovirus Host Interactions: EGFR and Host Cell Signaling Is a Point of Convergence Between Viral Infection and Functional Changes in Infected Cells

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