PMID- 27329558
OWN - NLM
STAT- MEDLINE
DCOM- 20180507
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Jun 22
TI  - Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-alpha-Mediated Activation of 
      NF-kappaB by targeting p65.
PG  - 28481
LID - 10.1038/srep28481 [doi]
LID - 28481
AB  - Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent 
      causing lower respiratory tract infections in young children worldwide. Nuclear 
      factor kappa B (NF-kappaB) transcription factors play crucial roles in clearance of 
      invading viruses through activation of many physiological processes. Previous 
      investigation showed that HBoV infection could significantly upregulate the level 
      of TNF-alpha which is a strong NF-kappaB stimulator. Here we investigated whether HBoV 
      proteins modulate TNF-alpha-mediated activation of the NF-kappaB signaling pathway. We 
      showed that HBoV NS1 and NS1-70 proteins blocked NF-kappaB activation in response to 
      TNF-alpha. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IkappaB kinase 
      alpha (IKKalpha)-, IkappaB kinase beta (IKKbeta)-, constitutively active mutant of IKKbeta 
      (IKKbeta SS/EE)-, or p65-induced NF-kappaB activation was inhibited by NS1 and NS1-70. 
      Furthermore, NS1 and NS1-70 didn't interfere with TNF-alpha-mediated IkappaBalpha 
      phosphorylation and degradation, nor p65 nuclear translocation. 
      Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 
      with p65. Of note, NS1 but not NS1-70 inhibited TNF-alpha-mediated p65 
      phosphorylation at ser536. Our findings together indicate that HBoV NS1 and 
      NS1-70 inhibit NF-kappaB activation. This is the first time that HBoV has been shown 
      to inhibit NF-kappaB activation, revealing a potential immune-evasion mechanism that 
      is likely important for HBoV pathogenesis.
FAU - Liu, Qingshi
AU  - Liu Q
AD  - Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious 
      Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, 
      China.
AD  - University of Chinese Academy of Sciences, Beijing 100049, China.
FAU - Zhang, Zhenfeng
AU  - Zhang Z
AD  - Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious 
      Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, 
      China.
FAU - Zheng, Zhenhua
AU  - Zheng Z
AD  - Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious 
      Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, 
      China.
FAU - Zheng, Caishang
AU  - Zheng C
AD  - Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious 
      Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, 
      China.
FAU - Liu, Yan
AU  - Liu Y
AD  - Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious 
      Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, 
      China.
FAU - Hu, Qinxue
AU  - Hu Q
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of 
      Sciences, Wuhan 430071, China.
FAU - Ke, Xianliang
AU  - Ke X
AD  - Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious 
      Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, 
      China.
FAU - Wang, Hanzhong
AU  - Wang H
AD  - Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious 
      Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160622
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (NF-kappa B)
RN  - 0 (NS1 protein, parvovirus)
RN  - 0 (RELA protein, human)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Viral Nonstructural Proteins)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - HEK293 Cells
MH  - Human bocavirus/genetics/immunology/*pathogenicity
MH  - Humans
MH  - NF-KappaB Inhibitor alpha/metabolism
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Parvoviridae Infections/immunology/virology
MH  - Phosphorylation
MH  - Proteolysis
MH  - Signal Transduction
MH  - Transcription Factor RelA/antagonists & inhibitors
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Viral Nonstructural Proteins/genetics/*immunology/physiology
PMC - PMC4916443
EDAT- 2016/06/23 06:00
MHDA- 2018/05/08 06:00
PMCR- 2016/06/22
CRDT- 2016/06/23 06:00
PHST- 2016/04/04 00:00 [received]
PHST- 2016/06/03 00:00 [accepted]
PHST- 2016/06/23 06:00 [entrez]
PHST- 2016/06/23 06:00 [pubmed]
PHST- 2018/05/08 06:00 [medline]
PHST- 2016/06/22 00:00 [pmc-release]
AID - srep28481 [pii]
AID - 10.1038/srep28481 [doi]
PST - epublish
SO  - Sci Rep. 2016 Jun 22;6:28481. doi: 10.1038/srep28481.