JVI Accepts, published online ahead of print on 29 August 2007

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J. Virol. doi:10.1128/JVI.01059-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Characterization of Hepatitis C Virus Deletion Mutants Circulating in Chronically Infected Patients

Suwanna Noppornpanth, Saskia L. Smits, Truong Xuan Lien, Yong Poovorawan, Albert D. M. E. Osterhaus, and Bart L. Haagmans^*

Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands; Department of Biological Analysis, Pasteur Institute Ho Chi Minh City, 167 Pasteur, Ho Chi Minh City, Vietnam; Center of Excellence in Viral Hepatitis Research, Department of Pediatrics, 10330 Rama IV, Chulalongkorn Hospital Bangkok, Thailand

^* To whom correspondence should be addressed. Email: b.haagmans{at}erasmusmc.nl.

Hepatitis C virus (HCV) has a linear positive-stranded RNA genome of 9600 nucleotides in length and displays a high level of sequence diversity caused by high mutation rates and recombination. However, when we performed long distance reverse transcription PCRs on HCV RNA isolated from serum of chronic HCV patients not only full-length HCV genomes but also HCV RNAs which varied in size from 7600 to 8346 nucleotides and contained large in frame deletions between E1 and NS2 were amplified. Carefully designed control experiments indicated that these deletion mutants are a bona fide natural RNA species, most likely packaged in virions. Moreover, deletion mutants were detected in sera of patients infected with different HCV genotypes. We observed that 7/37 (18.9%) of genotype 1, 5/43 (11.6%) of genotype 3 and 4/13 (30.7 %) of genotype 6 samples contained HCV deletion mutant genomes. These observations further exemplify HCV's huge genetic diversity and warrant studies to explore their biological relevance.

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