Nonmuscle Myosin Heavy Chain IIA Is a Critical Factor Contributing to the Efficiency of Early Infection of Severe Fever with Thrombocytopenia Syndrome Virus

Sun, Yinyan; Qi, Yonghe; Liu, Chenxuan; Gao, Wenqing; Chen, Pan; Fu, Liran; Peng, Bo; Wang, Haimin; Jing, Zhiyi; Zhong, Guocai; Li, Wenhui

doi:10.1128/jvi.02141-13

Cited by 104 publications

(110 citation statements)

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“…Previous studies demonstrated that HeLa cells were not susceptible to SFTSVpv and SFTSV infection (5,7). In this study, HeLa cells were weakly susceptible to infection with these viruses ( Fig.…”

Section: Discussionmentioning

confidence: 54%

“…Recently, it was reported that a C-type lectin, dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), is an initial binding receptor for SFTSV (5), as was previously reported for other phleboviruses (6). It was also reported that nonmuscle myosin heavy chain IIA is critical for the cellular entry of SFTSV (7). Analysis of the initial steps of SFTSV infection, including identification of the entry receptors and the role of viral GP in membrane fusion, may facilitate the development of entry inhibitors.…”

mentioning

confidence: 82%

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Characterization of Glycoprotein-Mediated Entry of Severe Fever with Thrombocytopenia Syndrome Virus

Tani

Shimojima

Fukushi

et al. 2016

J Virol

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with a high case fatality rate caused by SFTS virus (SFTSV). Effective vaccines and specific therapies for SFTS are urgently sought, and investigation into virus-host cell interactions is expected to contribute to the development of antiviral strategies. In this study, we have developed a pseudotype vesicular stomatitis virus (VSV) bearing the unmodified Gn/Gc glycoproteins (GPs) of SFTSV (SFTSVpv). We have analyzed the host cell entry of this pseudotype virus and native SFTSV. Both SFTSVpv and SFTSV exhibited high infectivity in various mammalian cell lines. The use of lysosomotropic agents indicated that virus entry occurred via pH-dependent endocytosis. SFTSVpv and SFTSV infectivity was neutralized by serial dilutions of convalescent-phase patient sera. Entry of SFTSVpv and growth of SFTSV were increased in Raji cells expressing not only the C-type lectin dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) but also DC-SIGN-related (DC-SIGNR) and liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin). 25-Hydroxycholesterol (25HC), a soluble oxysterol metabolite, inhibited the cell entry of SFTSVpv and the membrane fusion of SFTSV. These results indicate that pH-dependent endocytosis of SFTSVpv and SFTSV is enhanced by attachment to certain C-type lectins. SFTSVpv is an appropriate model for the investigation of SFTSV-GP-mediated cell entry and virus neutralization at lower biosafety levels. Furthermore, 25HC may represent a potential antiviral agent against SFTS. IMPORTANCESFTSV is a recently discovered bunyavirus associated with SFTS, a viral hemorrhagic fever with a high case fatality rate endemic to China, South Korea, and Japan. Because little is known about the characteristics of the envelope protein and entry mechanisms of SFTSV, further studies will be required for the development of a vaccine or effective therapies. In this study, we investigated the mechanism of SFTSV cell entry using SFTSVpv and the native virus. SFTSV can grow in nonsusceptible cell lines in the presence of certain C-type lectins. Moreover, 25HC, an oxysterol metabolite, may represent a potential therapeutic inhibitor of SFTSV infection. Severe fever with thrombocytopenia syndrome (SFTS), a newly recognized emerging viral infectious disease, is caused by a novel phlebovirus in the family Bunyaviridae, SFTS virus (SFTSV) (1-3). SFTSV can be transmitted to humans by tick bites, causing abrupt high fever, thrombocytopenia, leukopenia, and gastrointestinal symptoms, with a high case fatality rate (4). SFTSV is a single-stranded negative-sense RNA virus with three genomic segments, L, M, and S. The L segment encodes a viral RNA polymerase, while the M segment encodes the two viral envelope glycoproteins (GPs) Gn and Gc. The S segment is an ambisense RNA encoding a nucleoprotein (NP) and a nonstructural protein (NSs). The Gn and Gc proteins of bunyaviruses are usually localized in the Golgi app...

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Section: Discussionmentioning

confidence: 54%

mentioning

confidence: 82%

Characterization of Glycoprotein-Mediated Entry of Severe Fever with Thrombocytopenia Syndrome Virus

Tani

Shimojima

Fukushi

et al. 2016

J Virol

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“…Ailenin diğer üyeleri gibi negatif zincirli üç RNA segmenti içerir. Büyük segmenti L viral transkripsiyon ve replikasyonda rol oynayan RNA'ya bağımlı RNA polimeraz (RdRP) enzimini kodlar, orta büyüklükteki M segmenti bağı-şıklık ile ilgili olan ve "glikoprotein n" (Gn) ile "glikoprotein c" (Gc)'yi kodlayan bölgedir; diğerlerinden küçük olan S segmenti ise virüsün nükleoproteinleri (Np) ve yapısal olmayan proteinlerini (NSs) kodlar (18) .…”

Section: Trombositopeni Sendromlu Yüksek Ateş Virüsüunclassified

An overview of tick-borne viral pathogens in the light of current literature

Aktaş¹,

Aydın²

2017

TMCD

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An Overview of Tick-Borne Viral Pathogens in the Light of Current Literature Keywords: Tick-borne viruses, Heartland virus, CrimeanCongo hemorrhagic fever GiRiŞKenelere ilişkin ilk yazılara kene humması hakkında MÖ 1550 tarihli Mısır papirüslerinde rastlandığı, yazarı bilinen ilk yazıların ise MÖ 800 yılında Homeros tarafından yazıldığı sanılmaktadır (1) . Hastalıklarla ilişkisi yüzyıllar öncesinden bilinen keneler, insan ve hayvanlarda ölümle sonuçlanabilen çeşitli enfeksiyon etkenlerini taşımaları ile günümüze önemini arttırarak gelmişlerdir.Karasal omurgalı canlı gruplarının tüm sınıfları-nın zorunlu dış paraziti olan kenelerin tek besin

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“…Recently, NMHC-IIA was also reported to serve as an entry receptor for severe fever with thrombocytopenia syndrome virus (SFTSV) (30). Like HSV-1 entry, cell surface expression of NMHC-IIA was induced upon SFTSV infection (30). Moreover, NMHC-II activity for cellular protrusions such as filopodia, retraction fibers, and microvilli has been reported to be required for entry of several viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), papillomavirus, vaccinia virus, and murine leukemia virus (MLV) (31)(32)(33)(34).…”

mentioning

confidence: 99%

“…Cell surface expression of NMHC-IIA appears to be regulated by MLCK-mediated signaling events and to be required for efficient HSV-1 infection, based on the observations that (i) NM-IIA RLC phosphorylation as well as cell surface expression of NMHC-IIA upon HSV-1 entry is inhibited by ML-7, a specific inhibitor of MLCK, and (ii) ML-7 inhibits HSV-1 infection in vitro and in vivo (24). Recently, NMHC-IIA was also reported to serve as an entry receptor for severe fever with thrombocytopenia syndrome virus (SFTSV) (30). Like HSV-1 entry, cell surface expression of NMHC-IIA was induced upon SFTSV infection (30).…”

mentioning

confidence: 99%

Nonmuscle Myosin Heavy Chain IIB Mediates Herpes Simplex Virus 1 Entry

Arii

Hirohata

Kawaguchi

2015

J Virol

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IMPORTANCE Herpes simplex virus 1 (HSV-1) was reported to utilize nonmuscle myosin heavy chain IIA (NMHC-IIA) as an entry coreceptor associating with gB. Vertebrates have three genetically distinct isoforms of NMHC-II. In these isoforms, NMHC-IIB is of special interest since it highly expresses in neuronal tissue, one of the most important cellular targets of HSV-1 in vivo.In this study, we demonstrated that the ability to mediate HSV-1 entry appeared to be conserved in NMHC-II isoforms. These results may provide an insight into the mechanism by which HSV-1 infects a wide variety of cell types in vivo. Herpes simplex virus 1 (HSV-1) infects a wide variety of cultured cells in vitro, and two of the most important cellular targets for HSV-1 in vivo are epithelial cells at the initial site of infection and neurons for the establishment of latent infection (1). For HSV-1 entry into a cell, the initial interaction of HSV-1 with the cell is binding of virion envelope glycoprotein C (gC) and gB to cell surface glycosaminoglycans, preferentially heparan sulfate, which mediates virus attachment to the cell (2, 3). Although not essential for entry, this attachment provides a stable interaction between the virion and cell that facilitates the next entry steps (4). Subsequent viral penetration requires fusion between the virion envelope and host cell membrane and depends on gB, the heterodimer gH/gL, gD, and a gD receptor (5-7), which are thought to act in a cascade resulting in nucleocapsid entry into the cell (8-10). The gD receptors for HSV-1 reported to date fall into three classes (7): (i) HVEM (herpesvirus entry mediator), a member of the tumor necrosis factor (TNF) receptor family (11); (ii) nectin-1 and nectin-2, members of the immunoglobulin (Ig) superfamily (12, 13); and (iii) specific sites on heparan sulfate (3-O-S-HS) generated by certain 3-O-sulfotransferases (3-O-ST) (14). Studies using mice with HVEM and/or nectin-1 knocked out have elucidated the roles of gD receptors in viral replication and disease in vivo (15).Accumulating evidence supports the hypothesis that, in addition to the interaction of gD with a gD receptor, gB binding to a cellular receptor other than heparan sulfate is required for HSV-1 entry. These data include the following: (i) a soluble form of gB binds to heparan sulfate-deficient cells and blocks HSV-1 infection in some cell lines (16); (ii) paired Ig-like type 2 receptor ␣ (PILR␣), a paired receptor expressed mainly in immune cells (17)(18)(19), associates with gB and functions as an HSV-1 entry coreceptor (20); and (iii) HSV-1 infection of primary monocytes expressing both HVEM and PILR␣ is blocked by either an anti-HVEM or an anti-PILR␣ antibody (20). PILR␣ appears to play a significant role in viral replication and pathogenesis in vivo, based on the observation that mutation(s) in gB Thr-53 and/or Thr-480, residues required to have sialylated O-glycosylation for binding of gB to PILR␣ (21,22), abrogates PILR␣-dependent viral entry without affecting viral replication efficiency in PI...

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Nonmuscle Myosin Heavy Chain IIA Is a Critical Factor Contributing to the Efficiency of Early Infection of Severe Fever with Thrombocytopenia Syndrome Virus

Abstract: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus in the Bunyaviridae family. Most patients infected by SFTSV present with fever and thrombocytopenia, and up to 30% die due to multiple-organ dysfunction.

Cited by 104 publications

References 39 publications

Characterization of Glycoprotein-Mediated Entry of Severe Fever with Thrombocytopenia Syndrome Virus

Characterization of Glycoprotein-Mediated Entry of Severe Fever with Thrombocytopenia Syndrome Virus

An overview of tick-borne viral pathogens in the light of current literature

Nonmuscle Myosin Heavy Chain IIB Mediates Herpes Simplex Virus 1 Entry

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