Identification of 19 Novel Hepatitis C Virus Subtypes—Further Expanding HCV Classification

Abstract

Background Hepatitis C virus (HCV) is currently classified into 8 genotypes and 86 subtypes. The objective of this study was to characterize novel HCV subtypes and to investigate the impact of subtypes on treatment outcome. Methods Full-genome sequencing was performed on HCV plasma samples with <85% sequence homology of NS3, NS5A, and/or NS5B to HCV genotype (GT) 1–8 reference strains. Results A total of 14 653 patients with GT1–6 HCV infection were enrolled in clinical studies of sofosbuvir-based regimens. For the majority of the patients, a specific subtype could be assigned based on a close genetic relationship to previously described subtypes. However, for 19 patients, novel subtypes were identified with <85% homology compared with previously described subtypes. These novel subtypes had the following genotypes: 9 in GT2, 5 in GT4, 2 in GT6, and 1 each in GT1, GT3, and GT5. Despite the presence of polymorphisms at resistance-associated substitution positions, 18 of the 19 patients treated with sofosbuvir-containing therapy achieved SVR12. Conclusions Nineteen novel HCV subtypes were identified, suggesting an even greater genetic diversity of HCV subtypes than previously recognized.

Suboptimal SVR rates in African patients with atypical genotype 1 subtypes: Implications for global elimination of hepatitis C

“…18 Population-based studies to determine the frequency of unusual subtypes and the efficacy of DAA regimens against them, are urgently needed to formulate guidelines for treating HCV in Africa. 19 The corollary of these data, and the fact that in resource poor regions of Africa genotyping or full genome sequencing will not be available, is that second generation NS5A inhibitors should be preferred as first-line agents in the region. Use of second-line NS5A inhibitors seems to overcome resistance.…”

Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

“…HCV belongs to the Hepacivirus genus in the Flaviviridae family and comprises eight genotypes with at least 86 subtypes [10,11]. The virus particle is enveloped and has a single-stranded positive-sense RNA genome of approximately 9.6 kb, coding for one single open-reading frame that gives rise to 10 mature viral proteins [12].…”

Long-term virus evolution in nature

“…MV infection produces lifelong immunity (probably as a result of several factors) while patients that have cleared the hepatitis C virus (HCV) can be reinfected by the same virus. Cases of patients infected with HCVs of different genotypes and subtypes are increasingly identified, as more refined diagnostic tests are utilized, and the virus diversifies in nature (Hedskog et al, 2019).…”

“…Genotype differentiation is actually being witnessed during the expansion of HCV pandemics, partly due to a true genetic diversification of the virus as it circulated over the last decades, and partly due to increasing capacity of virus surveillance, and molecular and phylogenetic tools for genome analysis. The reader can find an illustration of this point by comparing the expanded phylogenetic HCV tree from six to seven genotypes and the subtype ramifications, published by P. Simmonds and colleagues in 1993[compare (Simmonds et al, 1993 and (Smith et al, 2014)], and continuing new subtype identification (Hedskog et al, 2019). Although it cannot be excluded that time might tend to equalize the number of serotypes among viruses, current evidence does not justify blaming differences in the extent of virus circulation to settle this issue.…”