Hepatitis C Virus Genotype 4: A Poorly Characterized Endemic Genotype

Globally, 13% of all hepatitis C virus (HCV) infections are caused by genotype 4 (GT4), which consists of 17 subtypes with various levels of susceptibility to anti-HCV therapy. This genotype is endemic in the Middle East and Africa and has considerably spread to Europe lately. The molecular features of HCV-GT4 infection, as well as its appropriate therapeutics, are poorly characterized as it has not been the subject of widespread basic research. As such, in this review, we aim to gather the current state of knowledge of this genotype with a particular emphasis on its heterogeneity, sequence signatures, resistance-associated substitutions, and available in vivo and in vitro models used for its study. We urge developing more cell-culture models based on different GT4 subtypes to better understand the virology and therapeutic response of this particular genotype. This review may raise more awareness about this genotype and trigger more basic research work to develop its research tools. This will be critical to design better therapeutics and help to provide adequate guidelines for physicians working with HCV-GT4 patients.