Varicella-zoster virus does not significantly induce cell defence mechanism mediated by the 2-5A/RNase L pathway during its replication cycle.
The 2-5A/RNase L pathway belongs to the antiviral system induced by interferon (IFN). RNase L is an inactive endoribonuclease which is activated by 2'-5' oligoadenylate (2-5A) synthesized by 2',5'-oligoadenylate synthetases. Once activated, RNase L cleaves mRNA, inhibiting the protein synthesis, as well as 28S and 18S ribosomal RNA (rRNA), leading to ribosomal inactivation. In this study, we investigate the role of the RNase L pathway as a cell defence mechanism during Varicella-zoster virus (VZV) replication, and the importance of a 68-kDa protein named RNase L inhibitor (RLI), which specifically inhibits RNase L. We demonstrate that the RNase L and RLI transcripts levels remain constant in VZV-infected cells for 24 h and 12 h, respectively, after which they decrease until the end of the viral cycle. VZV does not significantly modulate the protein level of RNase L during the course of infection. Using an rRNA cleavage assay to analyse the RNase L catalytic activity, we demonstrate that VZV replication leads to a minimal cleavage of rRNA. Moreover, the overexpression of RLI in a permissive cell line has no significant effect on the VZV replication. We conclude that RNase L does not constitute a major cell defence mechanism against the VZV infection.
Desloges
Nathalie
N
University of Witten/Herdecke, Institute of Microbiology and Virology, Germany.
Rahaus
Markus
M
Wolff
Manfred H
MH
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D045744:Cell Line, Tumor; D018833:Chaperonins / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism*; D014645:Herpesvirus 3, Human / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D012335:RNA, Ribosomal / Q000378:metabolism; D014779:Virus Replication
C501917:ABCE1 protein, human; D018528:ATP-Binding Cassette Transporters; D012335:RNA, Ribosomal; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D018833:Chaperonins