PMID- 23152531
OWN - NLM
STAT- MEDLINE
DCOM- 20130305
LR  - 20240104
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 87
IP  - 3
DP  - 2013 Feb
TI  - Cyclophilin inhibitors block arterivirus replication by interfering with viral 
      RNA synthesis.
PG  - 1454-64
LID - 10.1128/JVI.02078-12 [doi]
AB  - Virus replication strongly depends on cellular factors, in particular, on host 
      proteins. Here we report that the replication of the arteriviruses equine 
      arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus 
      (PRRSV) is strongly affected by low-micromolar concentrations of cyclosporine A 
      (CsA), an inhibitor of members of the cyclophilin (Cyp) family. In infected 
      cells, the expression of a green fluorescent protein (GFP) reporter gene inserted 
      into the PRRSV genome was inhibited with a half-maximal inhibitory concentration 
      (IC(50)) of 5.2 muM, whereas the GFP expression of an EAV-GFP reporter virus was 
      inhibited with an IC(50) of 0.95 muM. Debio-064, a CsA analog that lacks its 
      undesirable immunosuppressive properties, inhibited EAV replication with an 
      IC(50) that was 3-fold lower than that of CsA, whereas PRRSV-GFP replication was 
      inhibited with an IC(50) similar to that of CsA. The addition of 4 muM CsA after 
      infection prevented viral RNA and protein synthesis in EAV-infected cells, and 
      CsA treatment resulted in a 2.5- to 4-log-unit reduction of PRRSV or EAV 
      infectious progeny. A complete block of EAV RNA synthesis was also observed in an 
      in vitro assay using isolated viral replication structures. The small interfering 
      RNA-mediated knockdown of Cyp family members revealed that EAV replication 
      strongly depends on the expression of CypA but not CypB. Furthermore, upon 
      fractionation of intracellular membranes in density gradients, CypA was found to 
      cosediment with membranous EAV replication structures, which could be prevented 
      by CsA treatment. This suggests that CypA is an essential component of the viral 
      RNA-synthesizing machinery.
FAU - de Wilde, Adriaan H
AU  - de Wilde AH
AD  - Molecular Virology Laboratory, Department of Medical Microbiology, Center of 
      Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
FAU - Li, Yanhua
AU  - Li Y
FAU - van der Meer, Yvonne
AU  - van der Meer Y
FAU - Vuagniaux, Gregoire
AU  - Vuagniaux G
FAU - Lysek, Robert
AU  - Lysek R
FAU - Fang, Ying
AU  - Fang Y
FAU - Snijder, Eric J
AU  - Snijder EJ
FAU - van Hemert, Martijn J
AU  - van Hemert MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121114
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antiviral Agents)
RN  - 0 (RNA, Viral)
RN  - 0 (Viral Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 5.2.1.- (Cyclophilins)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*pharmacology
MH  - Cell Line
MH  - Cyclophilins/*antagonists & inhibitors
MH  - Cyclosporine/*pharmacology
MH  - Equartevirus/*physiology
MH  - Gene Knockdown Techniques
MH  - Genes, Reporter
MH  - Green Fluorescent Proteins/analysis/genetics
MH  - Inhibitory Concentration 50
MH  - Lepidoptera
MH  - Microbial Sensitivity Tests
MH  - Porcine respiratory and reproductive syndrome virus/*physiology
MH  - RNA, Viral/biosynthesis
MH  - Viral Proteins/biosynthesis
MH  - Virus Replication/*drug effects
PMC - PMC3554155
EDAT- 2012/11/16 06:00
MHDA- 2013/03/06 06:00
PMCR- 2013/08/01
CRDT- 2012/11/16 06:00
PHST- 2012/11/16 06:00 [entrez]
PHST- 2012/11/16 06:00 [pubmed]
PHST- 2013/03/06 06:00 [medline]
PHST- 2013/08/01 00:00 [pmc-release]
AID - JVI.02078-12 [pii]
AID - 02078-12 [pii]
AID - 10.1128/JVI.02078-12 [doi]
PST - ppublish
SO  - J Virol. 2013 Feb;87(3):1454-64. doi: 10.1128/JVI.02078-12. Epub 2012 Nov 14.