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Journal of Virology, November 2007, p. 12496-12503, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01059-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

Suwanna Noppornpanth,1 Saskia L. Smits,1 Truong Xuan Lien,2 Yong Poovorawan,3 Albert D. M. E. Osterhaus,1 and Bart L. Haagmans1*

Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands,1 Department of Biological Analysis, Pasteur Institute Ho Chi Minh City, 167 Pasteur, Ho Chi Minh City, Vietnam,2 Center of Excellence in Viral Hepatitis Research, Department of Pediatrics, Chulalongkorn Hospital, Rama IV, Bangkok 10330, Thailand3

Received 16 May 2007/ Accepted 20 August 2007

Hepatitis C virus (HCV) has a linear positive-stranded RNA genome of ~9,600 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 7,600 to 8,346 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.

* Corresponding author. Mailing address: Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. Phone: 31-104088004. Fax: 31-104089485. E-mail: b.haagmans{at}erasmusmc.nl

{triangledown} Published ahead of print on 29 August 2007.

Journal of Virology, November 2007, p. 12496-12503, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01059-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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