PMID- 26984731
OWN - NLM
STAT- MEDLINE
DCOM- 20170428
LR  - 20181113
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 90
IP  - 11
DP  - 2016 Jun 1
TI  - Characterization of Glycoprotein-Mediated Entry of Severe Fever with 
      Thrombocytopenia Syndrome Virus.
PG  - 5292-5301
LID - 10.1128/JVI.00110-16 [doi]
AB  - 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. 
      IMPORTANCE: SFTSV 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.
CI  - Copyright (c) 2016, American Society for Microbiology. All Rights Reserved.
FAU - Tani, Hideki
AU  - Tani H
AD  - Department of Virology I, National Institute of Infectious Diseases, Tokyo, 
      Japan.
FAU - Shimojima, Masayuki
AU  - Shimojima M
AD  - Department of Virology I, National Institute of Infectious Diseases, Tokyo, 
      Japan.
FAU - Fukushi, Shuetsu
AU  - Fukushi S
AD  - Department of Virology I, National Institute of Infectious Diseases, Tokyo, 
      Japan.
FAU - Yoshikawa, Tomoki
AU  - Yoshikawa T
AD  - Department of Virology I, National Institute of Infectious Diseases, Tokyo, 
      Japan.
FAU - Fukuma, Aiko
AU  - Fukuma A
AD  - Department of Virology I, National Institute of Infectious Diseases, Tokyo, 
      Japan.
FAU - Taniguchi, Satoshi
AU  - Taniguchi S
AD  - Department of Virology I, National Institute of Infectious Diseases, Tokyo, 
      Japan.
FAU - Morikawa, Shigeru
AU  - Morikawa S
AD  - Department of Veterinary Science, National Institute of Infectious Diseases, 
      Tokyo, Japan.
FAU - Saijo, Masayuki
AU  - Saijo M
AD  - Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan 
      msaijo@niid.go.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160512
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (CLEC4M protein, human)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Glycoproteins)
RN  - 0 (Hydroxycholesterols)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Viral Envelope Proteins)
RN  - 767JTD2N31 (25-hydroxycholesterol)
SB  - IM
MH  - Animals
MH  - Cell Adhesion Molecules/metabolism
MH  - Cell Line
MH  - China
MH  - Endocytosis
MH  - Glycoproteins/chemistry/*metabolism
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Hydroxycholesterols/pharmacology
MH  - Lectins, C-Type/metabolism
MH  - Neutralization Tests
MH  - Phlebotomus Fever/virology
MH  - Phlebovirus/chemistry/*physiology
MH  - Receptors, Cell Surface/metabolism
MH  - Thrombocytopenia/*virology
MH  - Vesicular stomatitis Indiana virus/drug effects/*genetics/growth & 
      development/*physiology
MH  - Viral Envelope Proteins/*metabolism
MH  - *Virus Internalization
PMC - PMC4934762
EDAT- 2016/03/18 06:00
MHDA- 2017/04/30 06:00
PMCR- 2016/11/12
CRDT- 2016/03/18 06:00
PHST- 2016/01/18 00:00 [received]
PHST- 2016/03/14 00:00 [accepted]
PHST- 2016/03/18 06:00 [entrez]
PHST- 2016/03/18 06:00 [pubmed]
PHST- 2017/04/30 06:00 [medline]
PHST- 2016/11/12 00:00 [pmc-release]
AID - JVI.00110-16 [pii]
AID - 00110-16 [pii]
AID - 10.1128/JVI.00110-16 [doi]
PST - epublish
SO  - J Virol. 2016 May 12;90(11):5292-5301. doi: 10.1128/JVI.00110-16. Print 2016 Jun 
      1.