PMID- 29444948
OWN - NLM
STAT- MEDLINE
DCOM- 20180517
LR  - 20201209
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 92
IP  - 9
DP  - 2018 May 1
TI  - The Superimposed Deubiquitination Effect of OTULIN and Porcine Reproductive and 
      Respiratory Syndrome Virus (PRRSV) Nsp11 Promotes Multiplication of PRRSV.
LID - 10.1128/JVI.00175-18 [doi]
LID - e00175-18
AB  - Linear ubiquitination plays an important role in the regulation of the immune 
      response by regulating nuclear factor kappaB (NF-kappaB). The linear 
      ubiquitination-specific deubiquitinase ovarian tumor domain deubiquitinase with 
      linear linkage specificity (OTULIN) can control the immune signaling transduction 
      pathway by restricting the Met1-linked ubiquitination process. In our study, the 
      porcine OTLLIN gene was cloned and deubiquitin functions were detected in a 
      porcine reproductive and respiratory syndrome virus (PRRSV)-infected-cell model. 
      PRRSV infection promotes the expression of the OTULIN gene; in turn, 
      overexpression of OTULIN contributes to PRRSV proliferation. There is negative 
      regulation of innate immunity with OTULIN during viral infection. The cooperative 
      effects of swine OTULIN and PRRSV Nsp11 potentiate the ability to reduce levels 
      of cellular protein ubiquitin associated with innate immunity. Importantly, PRRSV 
      Nsp11 recruits OTULIN through a nonenzymatic combination to enhance its ability 
      to remove linear ubiquitination targeting NEMO, resulting in a superimposed 
      effect that inhibits the production of type I interferons (IFNs). Our report 
      presents a new model of virus utilization of the ubiquitin-protease system in 
      vivo from the perspective of the viral proteins that interact with cell 
      deubiquitination enzymes, providing new ideas for prevention and control of 
      PRRSV.IMPORTANCE Deubiquitination effects of swine OTULIN were identified. The 
      interaction between porcine OTULIN and PRRSV Nsp11 is dependent on the OTU 
      domain. PRRSV Nsp11 recruits OTULIN through a nonenzymatic combination to promote 
      removal of linear ubiquitination targeting NEMO, resulting in a superimposed 
      effect that inhibits the production of type I IFNs.
CI  - Copyright (c) 2018 American Society for Microbiology.
FAU - Su, Yanxin
AU  - Su Y
AD  - School of Life Sciences, Tianjin University, Tianjin, China.
FAU - Shi, Peidian
AU  - Shi P
AD  - School of Life Sciences, Tianjin University, Tianjin, China.
FAU - Zhang, Lilin
AU  - Zhang L
AD  - School of Life Sciences, Tianjin University, Tianjin, China.
FAU - Lu, Dong
AU  - Lu D
AD  - School of Life Sciences, Tianjin University, Tianjin, China.
FAU - Zhao, Chengxue
AU  - Zhao C
AD  - School of Life Sciences, Tianjin University, Tianjin, China.
FAU - Li, Ruiqiao
AU  - Li R
AD  - School of Life Sciences, Tianjin University, Tianjin, China.
FAU - Zhang, Lei
AU  - Zhang L
AD  - School of Life Sciences, Tianjin University, Tianjin, China zhanglei@tju.edu.cn 
      jinhaih@tju.edu.cn.
FAU - Huang, Jinhai
AU  - Huang J
AD  - School of Life Sciences, Tianjin University, Tianjin, China zhanglei@tju.edu.cn 
      jinhaih@tju.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180413
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Interferon Type I)
RN  - 0 (Viral Nonstructural Proteins)
RN  - EC 3.1.- (Endoribonucleases)
RN  - EC 3.1.- (nidoviral uridylate-specific endoribonuclease)
RN  - EC 3.4.19.12 (Deubiquitinating Enzymes)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - Deubiquitinating Enzymes/genetics/*metabolism
MH  - Endoribonucleases
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Immunity, Innate/immunology
MH  - Interferon Type I/biosynthesis/*immunology
MH  - Porcine respiratory and reproductive syndrome 
      virus/*immunology/metabolism/*physiology
MH  - Protein Domains
MH  - Swine
MH  - Ubiquitination/*physiology
MH  - Viral Nonstructural Proteins/*metabolism
MH  - Virus Replication/*physiology
PMC - PMC5899196
OTO - NOTNLM
OT  - Nsp11
OT  - linear ubiquitination
OT  - porcine OTULIN
OT  - porcine reproductive and respiratory syndrome virus (PRRSV)
OT  - superimposed deubiquitination
EDAT- 2018/02/16 06:00
MHDA- 2018/05/18 06:00
PMCR- 2018/10/13
CRDT- 2018/02/16 06:00
PHST- 2018/02/08 00:00 [received]
PHST- 2018/02/12 00:00 [accepted]
PHST- 2018/02/16 06:00 [pubmed]
PHST- 2018/05/18 06:00 [medline]
PHST- 2018/02/16 06:00 [entrez]
PHST- 2018/10/13 00:00 [pmc-release]
AID - JVI.00175-18 [pii]
AID - 00175-18 [pii]
AID - 10.1128/JVI.00175-18 [doi]
PST - epublish
SO  - J Virol. 2018 Apr 13;92(9):e00175-18. doi: 10.1128/JVI.00175-18. Print 2018 May 
      1.