Activation of the 2-5OAS/RNase L pathway in CVB1 or HAV/18f infected FRhK-4 cells does not require induction of OAS1 or OAS2 expression.
The latent, constitutively expressed protein RNase L is activated in coxsackievirus and HAV strain 18f infected FRhK-4 cells. Endogenous oligoadenylate synthetase (OAS) from uninfected and virus infected cell extracts synthesizes active forms of the triphosphorylated 2-5A oligomer (the only known activator of RNase L) in vitro and endogenous 2-5A is detected in infected cell extracts. However, only the largest OAS isoform, OAS3, is readily detected throughout the time course of infection. While IFNbeta treatment results in an increase in the level of all three OAS isoforms in FRhK-4 cells, IFNbeta pretreatment does not affect the temporal onset or enhancement of RNase L activity nor inhibit virus replication. Our results indicate that CVB1 and HAV/18f activate the 2-5OAS/RNase L pathway in FRhK-4 cells during permissive infection through endogenous levels of OAS, but contrary to that reported for some picornaviruses, CVB1 and HAV/18f replication is insensitive to this activated antiviral pathway.
Kulka
Michael
M
Division of Molecular Biology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708, USA. michael.kulka@fda.hhs.gov
Calvo
Mona S
MS
Ngo
Diana T
DT
Wales
Samantha Q
SQ
Goswami
Biswendu B
BB
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D004722:Endoribonucleases / Q000378:metabolism*; D029822:Enterovirus B, Human / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology*; D004790:Enzyme Induction / Q000502:physiology*; D030041:Hepatitis A virus / Q000502:physiology*; D007372:Interferons; D007668:Kidney / Q000166:cytology; D008253:Macaca mulatta; D012330:RNA, Double-Stranded
D012330:RNA, Double-Stranded; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease