Hepatitis C virus RNA: dinucleotide frequencies and cleavage by RNase L.
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 1 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 1 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.
Washenberger
Christopher L
CL
Department of Microbiology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, United States.
Han
Jian-Qiu
JQ
Kechris
Katherina J
KJ
Jha
Babal Kant
BK
Silverman
Robert H
RH
Barton
David J
DJ
D001482:Base Composition / Q000235:genetics*; D003062:Codon / Q000235:genetics; D015226:Dinucleoside Phosphates / Q000235:genetics*; D004722:Endoribonucleases / Q000276:immunology / Q000378:metabolism*; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism*; D012641:Selection, Genetic
D003062:Codon; D015226:Dinucleoside Phosphates; D012367:RNA, Viral; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease