PMID- 34665110
OWN - NLM
STAT- MEDLINE
DCOM- 20211119
LR  - 20211123
IS  - 1465-2099 (Electronic)
IS  - 0022-1317 (Print)
IS  - 0022-1317 (Linking)
VI  - 102
IP  - 10
DP  - 2021 Oct
TI  - Viperin is anti-viral in vitro but is dispensable for restricting dengue virus 
      replication or induction of innate and inflammatory responses in vivo.
LID - 10.1099/jgv.0.001669 [doi]
LID - 001669
AB  - Viperin has antiviral function against many viruses, including dengue virus 
      (DENV), when studied in cells in culture. Here, the antiviral actions of viperin 
      were defined both in vitro and in a mouse in vivo model of DENV infection. Murine 
      embryonic fibroblasts (MEFs) derived from mice lacking viperin (vip(-/-)) showed 
      enhanced DENV infection, accompanied by increased IFN-beta and induction of ISGs; 
      IFIT1 and CXCL-10 but not IRF7, when compared to wild-type (WT) MEFs. In 
      contrast, subcutaneous challenge of immunocompetent WT and vip(-/-) mice with 
      DENV did not result in enhanced infection. Intracranial infection with DENV 
      resulted in body weight loss and neurological disease with a moderate increase in 
      mortality in vip(-/-) compared with WT mice, although this was not accompanied by 
      altered brain morphology, immune cell infiltration or DENV RNA level in the 
      brain. Similarly, DENV induction of IFN-beta, IFIT1, CXCL-10, IRF7 and TNF-alpha was not 
      significantly different in WT and vip(-/-) mouse brain, although there was a 
      modest but significant increase in DENV induction of IL-6 and IfI27la in the 
      absence of viperin. NanoString nCounter analysis confirmed no significant 
      difference in induction of a panel of inflammatory genes in WT compared to 
      vip(-/-) DENV-infected mouse brains. Further, polyI:C stimulation of bone 
      marrow-derived macrophages (BMDMs) induced TNF-alpha, IFN-beta, IL-6 and Nos-2, but 
      responses were not different in BMDMs generated from WT or vip(-/-) mice. Thus, 
      while there is significant evidence of anti-DENV actions of viperin in some cell 
      types in vitro, for DENV infection in vivo a lack of viperin does not affect 
      systemic or brain susceptibility to DENV or induction of innate and inflammatory 
      responses.
FAU - Al Shujairi, Wisam-Hamzah
AU  - Al Shujairi WH
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 
      Australia.
AD  - Department of Clinical Laboratory Sciences, College of Pharmacy, University of 
      Babylon, 51001 Hilla, Iraq.
FAU - Kris, Luke P
AU  - Kris LP
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 
      Australia.
FAU - van der Hoek, Kylie
AU  - van der Hoek K
AD  - School of Biological Sciences, Research Centre for Infectious Diseases, The 
      University of Adelaide, Adelaide, SA 5005, Australia.
FAU - Cowell, Evangeline
AU  - Cowell E
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 
      Australia.
FAU - Bracho-Granado, Gustavo
AU  - Bracho-Granado G
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 
      Australia.
FAU - Woodgate, Tahlia
AU  - Woodgate T
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 
      Australia.
FAU - Beard, Michael R
AU  - Beard MR
AD  - School of Biological Sciences, Research Centre for Infectious Diseases, The 
      University of Adelaide, Adelaide, SA 5005, Australia.
FAU - Carr, Jillian M
AU  - Carr JM
AD  - College of Medicine and Public Health, Flinders University, Adelaide, SA, 
      Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (Antiviral Agents)
RN  - 0 (Interferon Regulatory Factor-7)
RN  - 0 (Irf7 protein, mouse)
RN  - 0 (Proteins)
RN  - 0 (Rsad2 protein, mouse)
RN  - 77238-31-4 (Interferon-beta)
SB  - IM
MH  - Animals
MH  - *Antiviral Agents
MH  - Brain/immunology/virology
MH  - Cells, Cultured
MH  - Dengue/*immunology/*virology
MH  - Dengue Virus/*immunology/*physiology
MH  - *Immunity, Innate
MH  - Inflammation
MH  - Interferon Regulatory Factor-7/genetics
MH  - Interferon-beta/biosynthesis/genetics
MH  - Macrophages/immunology/metabolism
MH  - Mice
MH  - Proteins/genetics/*physiology
MH  - Virus Replication
PMC - PMC8604189
OTO - NOTNLM
OT  - dengue virus
OT  - inflammatory response
OT  - interferon response
OT  - neurovirulence
OT  - viperin
COIS- The authors declare that there are no conflicts of interest.
EDAT- 2021/10/20 06:00
MHDA- 2021/11/20 06:00
PMCR- 2021/10/19
CRDT- 2021/10/19 12:19
PHST- 2021/10/19 12:19 [entrez]
PHST- 2021/10/20 06:00 [pubmed]
PHST- 2021/11/20 06:00 [medline]
PHST- 2021/10/19 00:00 [pmc-release]
AID - 001669 [pii]
AID - 10.1099/jgv.0.001669 [doi]
PST - ppublish
SO  - J Gen Virol. 2021 Oct;102(10):001669. doi: 10.1099/jgv.0.001669.