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.

Keywords: Côte d'Ivoire; West Africa; hepatitis C virus; molecular epidemiology.

Fig. 1

Phylogenetic maximum likelihood tree constructed using NS5b sequences. Sequences determined in this study are shown in red. HCV1 and HCV2 are HCV genotypes 1 and 2, respectively. Reference sequences obtained from GenBank are shown in black. Bootstrap values higher than 70% are indicated on major branches. HCV subtype 1a and 1b are also shown.

Fig. 2

Phylogenetic maximum likelihood tree constructed using NS5b sequences from West and Central Africa. Sequences from Central Africa are marked with unfilled squares, and those from West Africa with black triangles. Sequences from Nigeria, West Africa are identified with blue filled triangles. The sequences from this study are marked with red filled circles. Bootstrap values higher than 70% are indicated on major branches.

Fig. 3

Phylogenetic maximum likelihood tree of intra-host HVR1 variants identified in 14 individuals infected with HCV1 and HCV2. All sequences from a single individual are shown using the sample identification code. The arrows indicate consensus HVR1 sequence. Bootstrap values higher than 70% are indicated on major branches.