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

Abstract

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.

The ribonuclease l‐dependent antiviral roles of human 2′,5′‐oligoadenylate synthetase family members against hepatitis C virus

“…The activation of RNase L without the further induction of OAS expression, as we have shown in JFH‐1 replicon cells, is not unique to HCV. It was reported that in the coxsackievirus or hepatitis A virus infection of monkey kidney FRhK‐4 cells, RNase L could be activated with no apparent induction of the OAS1 or OAS2 proteins; in these FRhK‐4 experiments, OAS3 was constitutively expressed at a relatively high level, and this expression level remained unchanged throughout the infection [31]. It appears likely that only a small quantity of OAS protein is needed as a catalytic enzyme for the activation of RNase L. Thus, constitutively expressed OAS1 and/or OAS3 might play a safeguard role through the activation of RNase L in the early stage of antiviral response against HCV infection.…”

Reduction of Hepatitis A Virus on FRhK‐4 Cells Treated with Korean Red Ginseng Extract and Ginsenosides

“…Kulka and others () demonstrated that HAV‐infected FRhK‐4 cells activate the 2’‐5'oligoadenylate synthetase/RNase L pathway. Activated RNase L degrades viral RNA and cellular single‐stranded RNA.…”

Characterization of CD8+ T-cell response in acute and resolved hepatitis A virus infection

“…The adaptive immune response seems to be sufficient despite the interference of HAV proteins with the innate immune response, e.g. IRF-3 [7,12,14] to clear the virus. Increased age is related to an increased HAV morbidity and mortality.…”