Hsv-1 Endocytic Entry into a Human Oligodendrocytic Cell Line Is Mediated by Clathrin and Dynamin but Not Caveolin

Praena, Beatriz; Bello-Morales, Raquel; López-Guerrero, José Antonio

doi:10.3390/v12070734

Cited by 20 publications

(13 citation statements)

References 80 publications

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“…However, the role of clathrin in entry into C10 or CHO-HVEM cells had not been assessed prior to this study. Moreover, recent work has suggested that HSV-1 entry into a human oligodendrocytic cell line (HOG) depends on clathrin ( 92 ). Therefore, HSV-1 may utilize CME in a cell-specific manner.…”

Section: Discussionmentioning

confidence: 99%

Contributions of the Four Essential Entry Glycoproteins to HSV-1 Tropism and the Selection of Entry Routes

Hilterbrand

Daly

Heldwein

2021

mBio

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Herpes simplex viruses (HSV-1 and HSV-2) encode up to 16 envelope proteins, four of which are essential for entry. However, whether these four proteins alone are sufficient to dictate the broad cellular tropism of HSV-1 and the selection of different cell type-dependent entry routes is unknown. To begin addressing this, we previously pseudotyped vesicular stomatitis virus (VSV), lacking its native glycoprotein G, with only the four essential entry glycoproteins of HSV-1: gB, gH, gL, and gD. This novel VSVΔG-BHLD pseudotype recapitulated several important features of HSV-1 entry: the requirement for gB, gH, gL, gD, and a cellular receptor and sensitivity to anti-gB and anti-gH/gL neutralizing antibodies. However, due to the use of a single cell type in that study, the tropism of the VSVΔG-BHLD pseudotype was not investigated. Here, we show that the cellular tropism of the pseudotype is severely limited compared to that of wild-type HSV-1 and that its entry pathways differ from the native HSV-1 entry pathways. To test the hypothesis that other HSV-1 envelope proteins may contribute to HSV-1 tropism, we generated a derivative pseudotype containing the HSV-1 glycoprotein C (VSVΔG-BHLD-gC) and observed a gC-dependent increase in entry efficiency in two cell types. We propose that the pseudotyping platform developed here has the potential to uncover functional contributions of HSV-1 envelope proteins to entry in a gain-of-function manner. IMPORTANCE Herpes simplex viruses (HSV-1 and HSV-2) contain up to 16 different proteins in their envelopes. Four of these, glycoproteins gB, gD, gH, and gL, are termed essential with regard to entry, whereas the rest are typically referred to as nonessential based on the entry phenotypes of the respective single genetic deletions. However, the single-gene deletion approach, which relies on robust loss-of-function phenotypes, may be confounded by functional redundancies among the many HSV-1 envelope proteins. We have developed a pseudotyping platform in which the essential four entry glycoproteins are isolated from the rest, which can be added back individually for systematic gain-of-function entry experiments. Here, we show the utility of this platform for dissecting the contributions of HSV envelope proteins, both the essential four and the remaining dozen (using gC as an example), to HSV entry.

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Section: Discussionmentioning

confidence: 99%

Contributions of the Four Essential Entry Glycoproteins to HSV-1 Tropism and the Selection of Entry Routes

Hilterbrand

Daly

Heldwein

2021

mBio

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“…Regarding viral infection, there are studies showing a dependence on both clathrin and cholesterol for cell entry, as in the case of varicella-zoster virus (VZV) ( Hambleton et al, 2007 ), type C food-and-mouth- disease virus (FMDV) ( Martín-Acebes et al, 2007 ), Crimea-Congo hemorrhagic fever virus (CCHFV) ( Simon et al, 2009 ), Japanese encephalitis virus (JEV) ( Yang et al, 2013 ) and HIV-1 ( Praena et al, 2020 ). Besides, viruses internalized by clathrin may require cholesterol and/or SM to escape from the endocytic vesicle via fusion.…”

Section: Membrane Rafts In Endocytosismentioning

confidence: 99%

Membrane Rafts: Portals for Viral Entry

et al. 2021

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Membrane rafts are dynamic, small (10–200 nm) domains enriched with cholesterol and sphingolipids that compartmentalize cellular processes. Rafts participate in roles essential to the lifecycle of different viral families including virus entry, assembly and/or budding events. Rafts seem to participate in virus attachment and recruitment to the cell surface, as well as the endocytic and non-endocytic mechanisms some viruses use to enter host cells. In this review, we will introduce the specific role of rafts in viral entry and define cellular factors implied in the choice of one entry pathway over the others. Finally, we will summarize the most relevant information about raft participation in the entry process of enveloped and non-enveloped viruses.

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“…This antipsychotic, brand name Thorazine in the United States, has been reported to have broad antiviral activity, including against the RNA viruses Chikungunya (CHIKV), 8 Crimean-Congo hemorrhagic virus (CCHFV), 8 Dengue (DENV), 9 Ebola (EBOV), 8 Hepatitis A (HepA), 10 Hepatitis C (HCV), 8,11 Human Immunodeficiency virus (HIV), 8 Human Parechovirus (HPEV-1), 12 Influenza, 13 Japanese Encephalitis Virus ( JEV), 8 Junin ( JV), 14 Measles, 15 Middle Eastern respiratory syndrome coronavirus (MERS-CoV), 8 Rabies (RABV), 16 SARS-CoV-1, 8 SARS-CoV-2, 5,8 Semliki Forest Virus (SFV), 8,17 Sindbis (SINV), 17 Vesicular Stomatitis (VSV), 8 West Nile Virus (WNV), 8 and Zika 8,18 ; and the DNA viruses Adenovirus, 19 Epstein-Barr (EBV), 20 Herpes Simplex (HSV-1, HSV-2), 21,22 Human Herpes (HHV-8), 23 Human Papilloma (HPV), 24 Human polyomavirus 2 also called John Cunningham ( JCV), 25 and Simian virus (SV40). 26…”

Section: The Most Extensive Information Is Available On Chlorpromazinementioning

confidence: 99%

“…HIV 8 In vitro Entry HPEV 12 In vitro Entry HPV-16 24 In vitro Entry HSV-1 21,22 In vitro Entry(cme)…”

Section: Model Site Of Viral Inhibitionmentioning

confidence: 99%

“…Multiple psychotropics have been shown to interfere with virus entry into the host cell by inhibition of clathrin-or caveolar-mediated endocytosis. 9,12,16,18,20,21,24,25,31,37,45,51 Several agents have been reported to interfere with virus/host fusion by intercalating into cholesterol-rich membrane domains. 11,44 A number of psychotropic agents appear to interfere with viral entry into host cells by destabilizing viral glycoprotein receptors.…”

Section: Unifying Mechanisms Of Actionmentioning

confidence: 99%

See 1 more Smart Citation

Repurposing Psychotropic Agents for Viral Disorders: Beyond Covid

Golden

Rosenstein

Belhorn

et al. 2021

ASSAY and Drug Development Technologies

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Recent reports have highlighted the possible role of the antipsychotic chlorpromazine and the antidepressant fluvoxamine as anti-coronavirus disease 2019 (COVID-19) agents. The objective of this narrative review is to explore what is known about the activity of psychotropic medications against viruses in addition to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PubMed was queried for ''drug repurposing, antiviral activity,'' and for ''antiviral activity'' with ''psychotropic drugs'' and individual agents, through November 2020. Of more than 100 psychotropic agents, 37 drugs, including 27 with a history of pediatric use were identified, which had been studied in the preclinical setting and found to have activity against viruses which are human pathogens. Effects were evaluated by type of virus and by category of psychotropic agent. Activity was identified both against viruses known to cause epidemics such as SARS-CoV-2 and Ebola and against those that are the cause of rare disorders such as Human Papillomatosis Virus-related respiratory papillomatosis. Individual drugs and classes of psychotropics often had activity against multiple viruses, with promiscuity explained by shared viral or cellular targets. Safety profiles of psychotropics may be more tolerable in this context than when they are used long-term in the setting of psychiatric illness. Nonetheless, translation of in vitro results to the clinical arena has been slow. Psychotropic medications as a class deserve further study, including in clinical trials for repurposing as antiviral drugs for children and adults.

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Hsv-1 Endocytic Entry into a Human Oligodendrocytic Cell Line Is Mediated by Clathrin and Dynamin but Not Caveolin

Cited by 20 publications

References 80 publications

Contributions of the Four Essential Entry Glycoproteins to HSV-1 Tropism and the Selection of Entry Routes

Contributions of the Four Essential Entry Glycoproteins to HSV-1 Tropism and the Selection of Entry Routes

Membrane Rafts: Portals for Viral Entry

Repurposing Psychotropic Agents for Viral Disorders: Beyond Covid

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