Complete genome analysis identifies recombinant events and positive selection sites of hepatitis C virus from mainland China during 2010–2019

Mixed Infections Unravel Novel HCV Inter-Genotypic Recombinant Forms within the Conserved IRES Region

“…As mentioned above, recombinant breakpoints within the HCV genome have been identified in both non-structural and structural regions, with a preference for occurrence between the core and NS2/NS3 regions, and specifically within the NS2/NS3 when the recombination event occurs between different genotypes [ 37 ]. To the best of our knowledge, our work and that of Qi et al (2021) [ 25 ] are the only studies to show inter-genotypic recombinant breakpoints within the IRES region. This infrequent finding is somewhat expected considering the critical role of the IRES in viral translation and its high degree of conservation.…”

“…In addition, although productive homologous and non-homologous recombination has been reported in vitro for HCV, inter-genotypic recombination seems infrequent [ 81 ]. Nevertheless, since 2002, several naturally occurring inter-genotypic HCV recombinants have been reported [ 15 , 16 , 17 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 29 , 30 , 31 , 33 ]. In this work, we report two inter-genotypic recombination forms involving genotypes 1a and 3a.…”

“…It can be hypothesized that continuous selection pressure in vivo results in an overall lower frequency of IRES recombinants. This may explain why only one inter-genotypic recombinant form has so far been detected in a consensus sequence derived from a patient (6a/3a) [ 25 ]. Our report is the first to detect 1a/3a and 3a/1a IRES recombinant forms, albeit as low-frequency variants within the viral intra-host population.…”

“…Nevertheless, several types of recombination have been reported over the years and have been categorized into three types: inter-genotype, inter-subtype, and intra-patient/intra-subtype recombination [ 14 ]. Previous research has identified eleven inter-genotype recombination types (2k/1b, 2i/6p, 2b/1b, 2/5, 2b/6w, 4/1, 3a/1b, 3a/1a, 2b/1a, 2a/1a, and 6a/3a) and seven inter-subtype recombination types (1b/1a, 1a/1c, 6a/6o, 6e/6o, 6e/6h, 6n/6o, and 4a/4d) based on either full-length or partial genome sequences [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Intra-patient recombination has also been reported [ 35 , 36 ], although it is more difficult to detect due to the genetic relatedness of the viral sequences.…”

“…An important point to mention is that most inter-genotype and inter-subtype recombination events have been detected when analyzing consensus sequences, whereas intra-patient recombinant detection has relied upon molecular cloning and/or next-generation sequencing, and in all cases evidenced favored intra-subtype recombination [ 37 ]. Breakpoints for recombination have been identified in various regions of the HCV genome, including non-structural and structural domains [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. While the full extent of recombination impact remains to be determined, it has been suggested that recombination accelerates viral adaptation by bringing together multiple advantageous mutations that may provide drug resistance or escape that may have profound implications for diagnosis, therapy, and epidemiology [ 38 ].…”