Serendipitous identification of natural Intergenotypic recombinants of hepatitis C in Ireland

Moreau Isabelle, Hegarty Susan, Levis John, Sheehy Patrick, Crosbie Orla, Kenny-Walsh Elizabeth, Fanning

Description

Recombination between hepatitis C single stranded RNA viruses is a rare event. Natural viable intragenotypic and intergenotypic recombinants between 1b-1a, 1a-1c and 2k-1b, 2i-6p, respectively, have been reported. Diagnostically recombinants represent an intriguing challenge. Hepatitis C genotype is defined by interrogation of the sequence composition of the 5' untranslated region [5'UTR]. Occasionally, ambiguous specimens require further investigation of the genome, usually by interrogation of the NS5B region. The original purpose of this study was to confirm the existence of a suspected mixed genotype infection of genotypes 2 and 4 by clonal analysis at the NS5B region of the genome in two specimens from two separate individuals. This initial identification of genotype was based on analysis of the 5'UTR of the genome by reverse line probe hybridisation [RLPH]. Results The original diagnosis of a mixed genotype infection was not confirmed by clonal analysis of the NS5B region of the genome. The phylogenetic analysis indicated that both specimens were natural intergenotypic recombinant forms of HCV. The recombination was between genotypes 2k and 1b for both specimens. The recombination break point was identified as occurring within the NS2 region of the genome. Conclusion The viral recombinants identified here resemble the recombinant form originally identified in Russia. The RLPH pattern observed in this study may be a signature indicative of this particular type of intergenotype recombinant of hepatitis C meriting clonal analysis of NS2.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2006
• Nombre de lectures: 394
• Langue: English

Extrait

Virology Journal

BioMedCentral

Open Access Research Serendipitous identification of natural Intergenotypic recombinants of hepatitis C in Ireland 1 11 1 Isabelle Moreau, Susan Hegarty, John Levis, Patrick Sheehy, 2 21 Orla Crosbie, Elizabeth KennyWalshand Liam J Fanning*

1 Address: MolecularVirology Diagnostic & Research Laboratory, Department of Medicine, Clinical Sciences Building, Cork University Hospital, 2 Cork, Ireland andDepartment of Gastroenterology, Cork University Hospital, Cork, Ireland Email: Isabelle Moreau  [e-mail]; Susan Hegarty  [e-mail]; John Levis  [e-mail]; Patrick Sheehy  [e-mail]; Orla Crosbie  [e-mail]; Elizabeth KennyWalsh  [e-mail]; Liam J Fanning*  [e-mail] * Corresponding author

Published: 15 November 2006Received: 20 September 2006 Accepted: 15 November 2006 Virology Journal2006,3:95 doi:10.1186/1743-422X-3-95 This article is available from: http://www.virologyj.com/content/3/1/95 © 2006 Moreau et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background:Recombination between hepatitis C single stranded RNA viruses is a rare event. Natural viable intragenotypic and intergenotypic recombinants between 1b-1a, 1a-1c and 2k-1b, 2i- 6p, respectively, have been reported. Diagnostically recombinants represent an intriguing challenge. Hepatitis C genotype is defined by interrogation of the sequence composition of the 5' untranslated region [5'UTR]. Occasionally, ambiguous specimens require further investigation of the genome, usually by interrogation of the NS5B region. The original purpose of this study was to confirm the existence of a suspected mixed genotype infection of genotypes 2 and 4 by clonal analysis at the NS5B region of the genome in two specimens from two separate individuals. This initial identification of genotype was based on analysis of the 5'UTR of the genome by reverse line probe hybridisation [RLPH]. Results:The original diagnosis of a mixed genotype infection was not confirmed by clonal analysis of the NS5B region of the genome. The phylogenetic analysis indicated that both specimens were natural intergenotypic recombinant forms of HCV. The recombination was between genotypes 2k and 1b for both specimens. The recombination break point was identified as occurring within the NS2 region of the genome. Conclusion:The viral recombinants identified here resemble the recombinant form originally identified in Russia. The RLPH pattern observed in this study may be a signature indicative of this particular type of intergenotype recombinant of hepatitis C meriting clonal analysis of NS2.

Background Hepatitis C virus infects approximately 170 million indi viduals' world wide [1]. Chronicity develops in 50–80% of infections [2,3]. Hepatitis C exists as a family of viruses, divided into 6 genotypes each with multiple subtypes [4]. The management and treatment of chronic hepatitis C

virus [HCV] is in part guided by the genotype of the infect ing virus [5,6]. The requirement for liver biopsy can be guided by genotype. Current therapeutic options of pegylated interferon and ribavirin have a population effi cacy of only 50% [7]. Genotype 2 and 3 respond with effi cacy of 80% in clinical trials. Duration of therapy is

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