Journal
VIRUS RESEARCH
Volume 130, Issue 1-2, Pages 85-95Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.virusres.2007.05.020
Keywords
interferon; 2-5A; innate immunity; hepatitis C virus; virus evolution; dinucleotide; RNase L; ribonuclease L
Categories
Funding
- NCI NIH HHS [R01 CA044059, CA-44059, R01 CA044059-23] Funding Source: Medline
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Ribonuclease L (RNase L) is an antiviral endoribonuclease that cleaves hepatitis C virus (HCV) RNA at single-stranded UA and UU dinucleotides throughout the open reading frame (ORF). To determine whether RNase L exerts evolutionary pressure on HCV we examined the frequencies of UA and UU dinucleotides in 162 RNA sequences from the Los Alamos National Labs HCV Database (http://hcv.lanl.gov). Considering the base composition of the HCV ORFs, both UA and UU dinucleotides were less frequent than predicted in each of 162 HCV RNAs. UA dinucleotides were significantly less frequent than predicted at each of the three codon positions while UU dinucleotides were less frequent than predicted predominantly at the wobble position of codons. UA and UU dinucleotides were among the least abundant dinucleotides in HCV RNA ORFs. Furthermore, HCV genotype I RNAs have a lower frequency of UA and UU dinucleotides than genotype 2 and 3 RNAs, perhaps contributing to increased resistance of HCV genotype 1 infections to interferon therapy. In vitro, RNase L cleaved both HCV genotype I and 2 RNAs efficiently. Thus, RNase L can cleave HCV RNAs efficiently and variably reduced frequencies of UA and UU dinucleotides in HCV RNA ORFs are consistent with the selective pressure of RNase L. (c) 2007 Elsevier B.V. All rights reserved.
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