Role of Proteolipid Protein in HSV-1 Entry in Oligodendrocytic Cells

Bello-Morales, Raquel; Crespillo, Antonio Jesús; Praena, Beatriz; Tabarés, E.; Revilla, Yolanda; García, Elena Martín; Fraile-Ramos, Alberto; Baron, Wia; Krummenacher, Claude; López-Guerrero, José Antonio

doi:10.1371/journal.pone.0147885

Cited by 7 publications

(7 citation statements)

References 40 publications

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“…Previous works carried out by our group have shown that OLs are highly susceptible to HSV-1 infection ( 40 ). Subsequent works revealed that oligodendrocyte precursor cells (OPCs) and cells of the human oligodendroglial HOG cell line cultured under differentiation conditions become more susceptible to HSV-1 ( 41 ), a fact that was consistent with the later finding that PLP, a myelin protein upregulated throughout differentiation, is involved in viral entry ( 42 ). These findings support the hypothesis that OLs might be a more susceptible target of HSV-1 infection in glial cells undergoing differentiation, a fact that could be relevant in HSV-1 pathogenicity.…”

Section: Introductionsupporting

confidence: 52%

Role of Microvesicles in the Spread of Herpes Simplex Virus 1 in Oligodendrocytic Cells

Bello-Morales

Praena

Nuez

et al. 2018

J Virol

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Herpes simplex virus 1 (HSV-1) is a neurotropic pathogen that can infect many types of cells and establishes latent infections in the neurons of sensory ganglia. In some cases, the virus spreads into the central nervous system, causing encephalitis or meningitis. Cells infected with several different types of viruses may secrete microvesicles (MVs) containing viral proteins and RNAs. In some instances, extracellular microvesicles harboring infectious virus have been found. Here we describe the features of shedding microvesicles released by the human oligodendroglial HOG cell line infected with HSV-1 and their participation in the viral cycle. Using transmission electron microscopy, we detected for the first time microvesicles containing HSV-1 virions. Interestingly, the Chinese hamster ovary (CHO) cell line, which is resistant to infection by free HSV-1 virions, was susceptible to HSV-1 infection after being exposed to virus-containing microvesicles. Therefore, our results indicate for the first time that MVs released by infected cells contain virions, are endocytosed by naive cells, and lead to a productive infection. Furthermore, infection of CHO cells was not completely neutralized when virus-containing microvesicles were preincubated with neutralizing anti-HSV-1 antibodies. The lack of complete neutralization and the ability of MVs to infect nectin-1/HVEM-negative CHO-K1 cells suggest a novel way for HSV-1 to spread to and enter target cells. Taken together, our results suggest that HSV-1 could spread through microvesicles to expand its tropism and that microvesicles could shield the virus from neutralizing antibodies as a possible mechanism to escape the host immune response.IMPORTANCE Herpes simplex virus 1 (HSV-1) is a neurotropic pathogen that can infect many types of cells and establishes latent infections in neurons. Extracellular vesicles are a heterogeneous group of membrane vesicles secreted by most cell types. Microvesicles, which are extracellular vesicles which derive from the shedding of the plasma membrane, isolated from the supernatant of HSV-1-infected HOG cells were analyzed to find out whether they were involved in the viral cycle. The importance of our investigation lies in the detection, for the first time, of microvesicles containing HSV-1 virions. In addition, virus-containing microvesicles were endocytosed into CHO-K1 cells and were able to actively infect these otherwise nonpermissive cells. Finally, the infection of CHO cells with these virus-containing microvesicles was not completely neutralized by anti-HSV-1 antibodies, suggesting that these extracellular vesicles might shield the virus from neutralizing antibodies as a possible mechanism of immune evasion.

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Section: Introductionsupporting

confidence: 52%

Role of Microvesicles in the Spread of Herpes Simplex Virus 1 in Oligodendrocytic Cells

Bello-Morales

Praena

Nuez

et al. 2018

J Virol

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“…Dilutions of anti-dynamin 2 were prepared in the presence of 10% human serum. Controls to assess labelling specificity included incubations with control primary antibodies or omission of the primary antibodies [24].…”

Section: Immunofluorescence Microscopymentioning

confidence: 99%

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

Praena

Bello-Morales

López-Guerrero

2020

Viruses

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Endocytosis is a pathway used by viruses to enter cells that can be classified based on the proteins involved, such as dynamin, clathrin or caveolin. Although the entry of herpes simplex type 1 (HSV-1) by endocytosis has been documented in different cell types, its dependence on clathrin has not been described whereas its dependence on dynamin has been shown according to the cell line used. The present work shows how clathrin-mediated endocytosis (CME) is one way that HSV-1 infects the human oligodendroglial (HOG) cell line. Partial dynamin inhibition using dynasore revealed a relationship between decrease of infection and dynamin inhibition, measured by viral titration and immunoblot. Co-localization between dynamin and HSV-1 was verified by immunofluorescence at the moment of viral entry into the cell. Inhibition by chlorpromazine revealed that viral progeny also decreased when clathrin was partially inhibited in our cell line. RT-qPCR of immediately early viral genes, specific entry assays and electron microscopy all confirmed clathrin’s participation in HSV-1 entry into HOG cells. In contrast, caveolin entry assays showed no effect on the entry of this virus. Therefore, our results suggest the participation of dynamin and clathrin during endocytosis of HSV-1 in HOG cells.

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“…Additionally, a mouse monoclonal antibody against PLP drastically inhibited HSV-1 entry into HOG cells. Moreover, PLP and virions were shown to colocalize by confocal and electron microscopy analyses, suggesting that PLP might be involved in HSV-1 entry in human oligodendrocytes [20].…”

Section: Herpes Simplex Virus Type 1 Tropismmentioning

confidence: 95%

“…Several cell receptors for viral entry have been described, but numerous observations suggest that more receptors for HSV-1 might exist. In [20], a novel role for the proteolipid protein (PLP) in HSV-1 entry into the human oligodendrocytic cell line human oligodendroglioma (HOG) has been proposed. Oligodendrocytes (OLs) are the glial cells that produce myelin, the electrically insulating layer that surrounds axons in the CNS [21].…”

Section: Herpes Simplex Virus Type 1 Tropismmentioning

confidence: 99%

Herpes Simplex Virus Type 1 at the Central Nervous System

Otth¹,

Acuña‐Hinrichsen²,

Leyton³

et al. 2016

Herpesviridae

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Herpes simplex virus type HSV-is a ubiquitous and neurotropic pathogen and is the most common cause of acute sporadic encephalitis in humans. This virus is characterized by establishing a persistent latent infection in neurons of its hosts for life. The pathogenic mechanisms of HSV-at the central nervous system CNS are not completely elucidated. Besides, evidences suggest that HSV-establish latency in the CNS in humans and that this condition would not be harmless, especially in people whose immune system is declined. This trait has been strongly suggested as a risk factor for the development of neurodegenerative pathologies such as Alzheimer's disease. Currently, it is unclear whether a neuron, which undergoes viral reactivation and produces infectious particles, survives and resumes latency, loses functionality, or is killed. These data highlight the need for more studies at cellular and molecular levels to understand the strategies used by the virus and the host cells during both productive and latent infection. The present chapter discusses the current investigations about HSV-infection at the CNS and the potential risk of neuronal dysfunction and chronic neurological diseases.

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Role of Proteolipid Protein in HSV-1 Entry in Oligodendrocytic Cells

Cited by 7 publications

References 40 publications

Role of Microvesicles in the Spread of Herpes Simplex Virus 1 in Oligodendrocytic Cells

Role of Microvesicles in the Spread of Herpes Simplex Virus 1 in Oligodendrocytic Cells

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

Herpes Simplex Virus Type 1 at the Central Nervous System

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