Virological surveillance, molecular phylogeny, and evolutionary dynamics of hepatitis C virus subtypes 1a and 4a isolates in patients from Saudi Arabia

Abstract

Hepatitis C virus (HCV) subtypes are pre-requisite to predict endemicity, epidemiology, clinical pathogenesis, diagnosis, and treatment of chronic hepatitis C infection. HCV genotypes 4 and 1 are the most prevalent in Saudi Arabia, however; less consensus data exist on circulating HCV subtypes in infected individuals. This study was aimed to demonstrate the virological surveillance, phylogenetic analysis, and evolutionary relationship of HCV genotypes 4 and 1 subtypes in the Saudi population with the rest of the world. Fifty-five clinical specimens from different parts of the country were analyzed based on 5′ untranslated region (5′ UTR) amplification, direct sequencing, and for molecular evolutionary genetic analysis. Pair-wise comparison and multiple sequence alignment were performed to determine the nucleotide conservation, nucleotide variation, and positional mutations within the sequenced isolates. The evolutionary relationship of sequenced HCV isolates with referenced HCV strains from the rest of the world was established by computing pairwise genetic distances and generating phylogenetic trees. Twelve new sequences were submitted to GenBank, NCBI database. The results revealed that HCV subtype 4a is more prevalent preceded by 1a in the Saudi population. Molecular phylogeny predicts the descendants’ relationship of subtype 4a isolates very close to Egyptian prototype HCV strains, while 1a isolates were homogeneous and clustering to the European and North American genetic lineages. The implications of this study highlight the importance of HCV subtyping as an indispensable tool to monitor the distribution of viral strains, to determine the risk factors of infection prevalence, and to investigate clinical differences of treatment outcomes among intergenotypic and intragenotypic isolates in the treated population.

Distribution of hepatitis C virus (HCV) genotypes in a Saudi Arabian hospital during the 2015-2020 period

“…A recent Saudi survey conducted in Jeddah has reported that there is a lower prevalence of GT-2 (4.1%) and higher HCV genotype 4 (60.7%) [1]. Because GT4 is very common in Egypt (10%-15%) and that many Egyptians work in Saudi Arabia thus it is assumed that GT4 arrived in Saudi Arabia with employees from Africa and the Middle East [2,7,9]. This is further supported by the sequencing of the HCV core region [15].…”

“…Chronic HCV infection accounts for 20% of hepatocellular carcinoma (HCC), and about 700,000 people die annually from complications related to HCV [6]. HCV is classified into seven genotypes (GT) and 67 subtypes such as 1a, 1b, 2a, 3a, 4a [3,7]. Globally, GT-1 is common in North America, South America, Western and Northern Europe, representing 46% of all HCV cases [7].…”

“…HCV is classified into seven genotypes (GT) and 67 subtypes such as 1a, 1b, 2a, 3a, 4a [3,7]. Globally, GT-1 is common in North America, South America, Western and Northern Europe, representing 46% of all HCV cases [7]. GT-3 is common in South Asia, Australia, and some parts of Western Europe and represents 30% of all HCV [7].…”

“…Globally, GT-1 is common in North America, South America, Western and Northern Europe, representing 46% of all HCV cases [7]. GT-3 is common in South Asia, Australia, and some parts of Western Europe and represents 30% of all HCV [7]. GT-2 is common in West Africa and South America and common also in Japan, some parts of Europe, and North America [3,7].…”

“…GT-3 is common in South Asia, Australia, and some parts of Western Europe and represents 30% of all HCV [7]. GT-2 is common in West Africa and South America and common also in Japan, some parts of Europe, and North America [3,7]. GT-4 and GT-6 are common in Central/North Africa and East/ Southern Asia, respectively [3].…”