Hepatitis C virus genetic variability and evolution

Abstract

Hepatitis C virus (HCV) has infected over 170 million people worldwide and creates a huge disease burden due to chronic, progressive liver disease. HCV is a singlestranded, positive sense, RNA virus, member of the Flaviviridae family. The high error rate of RNA-dependent RNA polymerase and the pressure exerted by the host immune system, has driven the evolution of HCV into 7 different genotypes and more than 67 subtypes. HCV evolves by means of different mechanisms of genetic variation. On the one hand, its high mutation rates generate the production of a large number of different but closely related viral variants during infection, usually referred to as a quasispecies. The great quasispecies variability of HCV has also therapeutic implications since the continuous generation and selection of resistant or fitter variants within the quasispecies spectrum might allow viruses to escape control by antiviral drugs. On the other hand HCV exploits recombination to ensure its survival. This enormous viral diversity together with some host factors has made it difficult to control viral dispersal. Current treatment options involve pegylated interferon-α and ribavirin as dual therapy or in combination with a direct-acting antiviral drug, depending on the country. Despite all the efforts put into antiviral therapy studies, eradication of the virus or the development of a preventive vaccine has been unsuccessful so far. This review focuses on current available data reported to date on the genetic mechanisms driving the molecular evolution of HCV populations and its relation with the antiviral therapies designed to control HCV infection. Hepatitis C virus genetic variability and evolution no preventive vaccine, and though antiviral therapy has been improved in the past few years, not all patients eradicate the virus as a result of it. The main reason lies in the intrinsic genetic variability that characterises RNA viruses, such as HCV, whose RNA polymerase lacks proof-reading activity, leading to a high mutation rate and the generation of a wide range of genome variants better known as a quasispecies. Therefore this review summarises current data on HCV quasispecies dynamics, antiviral therapy and recombination events.Echeverría N, Moratorio G, Cristina J, Moreno P. Hepatitis C virus genetic variability and evolution. World J Hepatol 2015; 7(6): 831845 Available from:

Research gaps in viral hepatitis

“…No prophylactic vaccine is available for HCV infection, while the virus’ genetic variability and capacity to escape host immune responses make vaccine development a formidable challenge . Recent findings on the viral envelope structure and innovative experimental animal models have uncovered new opportunities for HCV vaccine research .…”

Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database

“…The presence of HCV mutations is mainly due to factors such as selection pressure, error-prone replication (because of RNA polymerase’s poor fidelity) and the high replication capacity of the virus. It is believed that any mutant can be generated continuously in a HCV-infected patient[17]. Hence, selected variants are considered to be pre-existent mutants generated during the natural HCV life cycle.…”

Distribution of hepatitis C genotypes in Uttar Pradesh, India; rare genotype 4 detected

“…Since HCV core gene is highly conserved between different GTs, therefore we preferred core region for genotyping . Region wise HCV genotyping study is important because it provides information with respect to strain variations and potential association with disease severity …”