Intra‐host diversity and evolution of hepatitis C virus endemic to Côte d'Ivoire

Abstract

Hepatitis C virus (HCV) infection presents an important, but underappreciated public health problem in Africa. In Côte d’Ivoire, very little is known about the molecular dynamics of HCV infection. Plasma samples (n = 608) from pregnant women collected in 1995 from Côte d’Ivoire were analyzed in this study. Only 18 specimens (~3%) were found to be HCV PCR-positive. Phylogenetic analysis of the HCV NS5b sequences showed that the HCV variants belong to genotype 1 (HCV1) (n = 12, 67%) and genotype 2 (HCV2) (n = 6, 33%), with a maximum genetic diversity among HCV variants in each genotype being 20.7% and 24.0%, respectively. Although all HCV2 variants were genetically distant from each other, six HCV1 variants formed two tight sub-clusters belonging to HCV1a and HCV1b. Analysis of molecular variance (AMOVA) showed that the genetic structure of HCV isolates from West Africa with Côte d’Ivoire included were significantly different from Central African strains (P = 0.0001). Examination of intra-host viral populations using next-generation sequencing of the HCV HVR1 showed a significant variation in intra-host genetic diversity among infected individuals, with some strains composed of sub-populations as distant from each other as viral populations from different hosts. Collectively, the results indicate a complex HCV evolution in Côte d’Ivoire, similar to the rest of West Africa, and suggest a unique HCV epidemic history in the country.

A re-evaluation of the origin of hepatitis C virus genotype 2 in West Africa

“…Instead, its frequency fluctuates. Among all HCV strains from West Africa, HCV2 was found in 85% of cases in Guinea, Guinea-Bissau (Markov et al , 2009) and Ghana (Layden et al , 2015), and only in 33, 25 and 15% (Forbi et al , 2012, 2014; Markov et al , 2009) of cases in Côte d’Ivoire, Cameron and Nigeria, respectively. Thus, the countries of Guinea and Ghana with the highest HCV2 frequency are separated by Côte d’Ivoire with a low HCV2 frequency, which is inconsistent with the west-to-east gradient of HCV2 frequency proposed earlier.…”

“…However, the introduction of other HCV genotypes, e.g. genotype 1 in Côte d’Ivoire (Forbi et al , 2014) and Nigeria (Forbi et al , 2012), might influence HCV2 prevalence in these countries by displacing HCV2 as the dominant genotype.…”

“…This resulted in the isolation of six HCV2 sequences with GenBank accession numbers KC012573, KC012577, KC012578, KC012585, KC012587 and KC012588. Additional details can be found in Forbi et al (2014).…”

Accurate Genetic Detection of Hepatitis C Virus Transmissions in Outbreak Settings

“…However, this study shows that genetic distances among HCV strains using a single sequence result in less accurate separation of related and unrelated cases. Moreover, consensus sequences obtained by direct sequencing are rarely identical to the major variant and frequently different from any sequence variant sampled from a specimen [29, 33], indicating that consensus sequences result from amalgamation of a heterogeneous viral population and should be used for the detection of transmission with caution.…”

“…A large sample of intra-host viral variants obtained using NGS represents more adequately intra-host viral subpopulations and their minority variants, thus, improving accuracy of genetic detection of transmissions [27, 29, 30]. However, sampling thousands of intra-host HCV variants complicates phylogenetic analysis, straining computational resources, being time-consuming and difficult to interpret.…”