PMID- 33990004
OWN - NLM
STAT- MEDLINE
DCOM- 20210902
LR  - 20210902
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 135
DP  - 2021 Jul
TI  - Functionally active cyclin-dependent kinase 9 is essential for porcine 
      reproductive and respiratory syndrome virus subgenomic RNA synthesis.
PG  - 351-364
LID - S0161-5890(21)00155-3 [pii]
LID - 10.1016/j.molimm.2021.05.004 [doi]
AB  - Cyclin-dependent kinase 9 (CDK9) is a key regulator of RNA-polymerase II and a 
      candidate therapeutic target for various virus infections such as respiratory 
      syncytial virus, herpes simplex virus, human adenovirus, human cytomegalovirus, 
      hepatitis virus B, and human papillomavirus. We employed CDK9-IN-1, a selective 
      CDK9 inhibitor, to investigate the role of CDK9 in porcine reproductive and 
      respiratory syndrome virus (PRRSV) infection. CDK9-IN-1 dose-dependently reduced 
      PRRSV replication without cytotoxicity in the infected cells. The antiviral 
      activity of CDK9-IN-1 was further confirmed by evaluating the effects of 
      lentivirus-mediated CDK9 knockdown or CDK9 overexpression on PRRSV infection. 
      Briefly, the depletion of CDK9 significantly inhibited viral replication, while 
      the overexpression of CDK9 promoted viral replication. PRRSV infection also 
      enhanced the nuclear export of CDK9 without affecting CDK9 protein expression. 
      Viral replication cycle analyses further revealed that functionally active CDK9 
      in the cytosol advanced viral subgenomic RNA synthesis. Collectively, our data 
      illustrated that CDK9 was a new host factor that was involved in PRRSV subgenomic 
      RNA synthesis, and CDK9 inhibitor, CDK9-IN-1 was a promising antiviral candidate 
      for PRRSV infection.
CI  - Copyright (c) 2021. Published by Elsevier Ltd.
FAU - Wang, Meng-Di
AU  - Wang MD
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 
      Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of 
      Agriculture and Rural Affairs of the People's Republic of China, China; 
      International Joint Research Center of National Animal Immunology, Henan 
      Agricultural University, Zhengzhou, Henan Province, China; Henan University of 
      Animal Husbandry and Economy, Zhengzhou, Henan Province, China.
FAU - Yang, Le
AU  - Yang L
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 
      Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of 
      Agriculture and Rural Affairs of the People's Republic of China, China.
FAU - Meng, Jie-Jie
AU  - Meng JJ
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 
      Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of 
      Agriculture and Rural Affairs of the People's Republic of China, China.
FAU - Pan, Jia-Jia
AU  - Pan JJ
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 
      Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of 
      Agriculture and Rural Affairs of the People's Republic of China, China.
FAU - Zhang, Chao
AU  - Zhang C
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 
      Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of 
      Agriculture and Rural Affairs of the People's Republic of China, China.
FAU - Wan, Bo
AU  - Wan B
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 
      Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of 
      Agriculture and Rural Affairs of the People's Republic of China, China; 
      International Joint Research Center of National Animal Immunology, Henan 
      Agricultural University, Zhengzhou, Henan Province, China.
FAU - Sun, Yu
AU  - Sun Y
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 
      Province, China.
FAU - Wang, Jiang
AU  - Wang J
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 
      Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of 
      Agriculture and Rural Affairs of the People's Republic of China, China; 
      International Joint Research Center of National Animal Immunology, Henan 
      Agricultural University, Zhengzhou, Henan Province, China.
FAU - Chu, Bei-Bei
AU  - Chu BB
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 
      Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of 
      Agriculture and Rural Affairs of the People's Republic of China, China; 
      International Joint Research Center of National Animal Immunology, Henan 
      Agricultural University, Zhengzhou, Henan Province, China. Electronic address: 
      chubeibe@henau.edu.cn.
FAU - Zhang, Gai-Ping
AU  - Zhang GP
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan 
      Province, China; International Joint Research Center of National Animal 
      Immunology, Henan Agricultural University, Zhengzhou, Henan Province, China. 
      Electronic address: zhanggaip@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210511
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Antiviral Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Viral)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 9)
SB  - IM
MH  - Active Transport, Cell Nucleus/physiology
MH  - Animals
MH  - Antiviral Agents/*pharmacology
MH  - Cell Line
MH  - Cyclin-Dependent Kinase 9/*antagonists & inhibitors/genetics/metabolism
MH  - Genome, Viral/genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Porcine respiratory and reproductive syndrome virus/*genetics
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA Interference
MH  - RNA, Viral/*biosynthesis/genetics
MH  - Swine
MH  - Virus Replication/*drug effects
OTO - NOTNLM
OT  - CDK9
OT  - PRRSV
OT  - Subgenomic RNA
OT  - Viral replication
EDAT- 2021/05/15 06:00
MHDA- 2021/09/03 06:00
CRDT- 2021/05/14 20:23
PHST- 2021/01/20 00:00 [received]
PHST- 2021/04/20 00:00 [revised]
PHST- 2021/05/06 00:00 [accepted]
PHST- 2021/05/15 06:00 [pubmed]
PHST- 2021/09/03 06:00 [medline]
PHST- 2021/05/14 20:23 [entrez]
AID - S0161-5890(21)00155-3 [pii]
AID - 10.1016/j.molimm.2021.05.004 [doi]
PST - ppublish
SO  - Mol Immunol. 2021 Jul;135:351-364. doi: 10.1016/j.molimm.2021.05.004. Epub 2021 
      May 11.