Serendipitous identification of natural Intergenotypic recombinants of hepatitis C in Ireland

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].

Recent evidence of underestimated circulation of hepatitis C virus intergenotypic recombinant strain RF2k/1b in the Rhône-Alpes region, France, January to August 2014: implications for antiviral treatment

“…No RF was detected in any of these patients; however, it cannot be excluded that this strain has spread outside of the Caucasus population. Indeed, the spread of these RF in Western European countries is poorly described and only a few previous reported cases of HCV RF2k/1b are available in studies from Cyprus, France, Ireland and the Netherlands [6][7][8][9]. In all these cases, the patients had their origin in Russia or Georgia.…”

Naturally Occurring Hepatitis C Virus Subgenomic Deletion Mutants Replicate Efficiently in Huh-7 Cells and Are trans -Packaged In Vitro To Generate Infectious Defective Particles

“…Because of this huge genetic diversity, HCV is currently classified into six major genotypes and more than 80 subtypes (44). Recombination may be another mechanism exploited by HCV to increase genetic diversity: naturally occurring intergenotypic recombinant viruses that often have their recombination points in the trans-membrane domains of NS2 were recently identified (20,21,26,27,33,35).…”

“…Because of this huge genetic diversity, HCV is currently classified into six major genotypes and more than 80 subtypes (44). Recombination may be another mechanism exploited by HCV to increase genetic diversity: naturally occurring intergenotypic recombinant viruses that often have their recombination points in the trans-membrane domains of NS2 were recently identified (20,21,26,27,33,35).Recent publications have reported the presence of natural HCV subgenomic RNAs in serum and liver of infected patients, mostly containing large in-frame deletions from E1 up to NS2, always found together with the full-length wild-type (wt) RNAs (5,16,36,54). These mutant viral genomes persist for a long time (at least 2 years), and sequence analysis suggests that subgenomic (the predominant species during this period) and full-length HCV evolve independently (54).…”

Heterogeneous genomic locations within NS3, NS4A and NS4B identified for genotyping and subtyping of Hepatitis C virus: A simple genome analysis approach

“…This method accurately identifies subtypes and provides evolutionary information that is used to establish an epidemiological picture of circulating variants (Smith et al, 2014;Pybus et al, 2009). Although sequencing only in core or NS5B is considered sufficient for subtype identification, recombinants can only be typed by whole genome sequencing (Kalinina et al, 2002;Nakano et al, 2012;Kurbanov et al, 2008aKurbanov et al, , 2008bMoreau et al, 2006;Morel et al, 2010;Tallo et al, 2007). It can be contemplated that multiple sequencing sites distinctly apart may eliminate the need for whole genome sequencing, in case of recombinants.…”