PMID- 35293774
OWN - NLM
STAT- MEDLINE
DCOM- 20220415
LR  - 20220917
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 96
IP  - 7
DP  - 2022 Apr 13
TI  - Host Cells Actively Resist Porcine Reproductive and Respiratory Syndrome Virus 
      Infection via the IRF8-MicroRNA-10a-SRP14 Regulatory Pathway.
PG  - e0000322
LID - 10.1128/jvi.00003-22 [doi]
LID - e00003-22
AB  - MicroRNAs (miRNAs) play an important role in the virus-host interaction. Our 
      previous work has indicated that the expression level of miR-10a increased in 
      porcine alveolar macrophages (PAMs) during porcine reproductive and respiratory 
      syndrome virus (PRRSV) infection and further inhibited viral replication through 
      downregulates the expression of host molecule signal-recognition particle 14 
      (SRP14) protein. However, the molecular mechanism of miR-10a increased after 
      PRRSV infection remains unknown. In the present study, transcription factor 
      interferon regulatory factor 8 (IRF8) was identified as a negative regulator of 
      miR-10a. PRRSV infection decreases the expression level of IRF8 in PAMs, leading 
      to upregulating miR-10a expression to play an anti-PRRSV role. Meanwhile, this 
      work first proved that IRF8 promoted PRRSV replication in an miR-10a-dependent 
      manner. Further, we explained that SRP14, the target gene of miR-10a, promotes 
      the synthesis of the PRRSV genome by interacting with the viral components Nsp2, 
      thus facilitating PRRSV replication. In conclusion, we identified a novel 
      IRF8-miR-10a-SRP14 regulatory pathway against PRRSV infection, which provides new 
      insights into virus-host interactions and suggests potential new antiviral 
      strategies to control PRRSV. IMPORTANCE Porcine reproductive and respiratory 
      syndrome virus (PRRSV) has rapidly spread to the global pig industry and caused 
      incalculable economic damage since first discovered in the 1980s. However, 
      conventional vaccines do not provide satisfactory protection. Understanding the 
      molecular mechanisms of host resistance to PRRSV infection is necessary to 
      develop safe and effective strategies to control PRRSV. During viral infection, 
      miRNAs play vital roles in regulating the expression of viral or host genes at 
      the posttranscriptional level. The significance of our study is that we revealed 
      the transcriptional regulation mechanism of the antiviral molecule miR-10a after 
      PRRSV infection. Moreover, our research also explained the mechanism of host 
      molecule SRP14, the target gene of miR-10a regulating PRRSV replication. Thus, we 
      report a novel regulatory pathway of IRF8-miR-10a-SRP14 against PRRSV infection, 
      which provides new insights into virus-host interactions and suggests potential 
      new control measures for future PRRSV outbreaks.
FAU - Zheng, Zifang
AU  - Zheng Z
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 
      China.
FAU - Fu, Xiali
AU  - Fu X
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 
      China.
FAU - Ling, Xue
AU  - Ling X
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 
      China.
FAU - Sun, Huanhuan
AU  - Sun H
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 
      China.
FAU - Li, Yang
AU  - Li Y
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 
      China.
FAU - Ma, Zhiqian
AU  - Ma Z
AD  - State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary 
      Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, 
      China.
FAU - Wei, Bingjie
AU  - Wei B
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 
      China.
FAU - Zheng, Haixue
AU  - Zheng H
AUID- ORCID: 0000-0001-6850-1379
AD  - State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary 
      Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, 
      China.
FAU - Xiao, Shuqi
AU  - Xiao S
AUID- ORCID: 0000-0002-6468-2608
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20220316
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antiviral Agents)
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (MicroRNAs)
RN  - 0 (interferon regulatory factor-8)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/metabolism
MH  - Cell Line
MH  - Gene Expression Regulation/immunology
MH  - Host Microbial Interactions/immunology
MH  - Interferon Regulatory Factors/genetics/immunology
MH  - Macrophages, Alveolar
MH  - *MicroRNAs/genetics/immunology
MH  - *Porcine Reproductive and Respiratory Syndrome/immunology/virology
MH  - *Porcine respiratory and reproductive syndrome virus/genetics/immunology
MH  - Swine
MH  - Virus Replication/genetics
PMC - PMC9006959
OTO - NOTNLM
OT  - IRF8
OT  - PRRSV
OT  - SRP14
OT  - miR-10a
OT  - transcriptional regulation
COIS- The authors declare no conflict of interest.
EDAT- 2022/03/17 06:00
MHDA- 2022/04/16 06:00
PMCR- 2022/09/16
CRDT- 2022/03/16 12:12
PHST- 2022/03/17 06:00 [pubmed]
PHST- 2022/04/16 06:00 [medline]
PHST- 2022/03/16 12:12 [entrez]
PHST- 2022/09/16 00:00 [pmc-release]
AID - 00003-22 [pii]
AID - jvi.00003-22 [pii]
AID - 10.1128/jvi.00003-22 [doi]
PST - ppublish
SO  - J Virol. 2022 Apr 13;96(7):e0000322. doi: 10.1128/jvi.00003-22. Epub 2022 Mar 16.