Identification of two novel hepatitis C virus subtype 2 from Tunisia (2v and 2w)

Background Hepatitis C virus (HCV) has a high genetic diversity. Eight genotypes and 90 subtypes are currently described. Genotypes are clinically significant for therapeutic management and their determination is necessary for epidemiological studies. Methods Tunisian patients plasma samples (n = 6) with unassigned HCV-2 subtype using partial sequencing in the NS5B and Core/E1 regions were analyzed by realizing whole-genome sequencing analysis. Phylogenetic analyses were performed to assign subtypes. Results Phylogenetic analysis of the full genome sequences of Tunisian strains shows two subtypes within HCV-2. These later were genetically distinct from all previously established HCV-2 subtypes with nucleotide divergence greater than 15% (20% -31%). These two subtypes are proposed as new subtypes 2v and 2w. Conclusions The discovery of two new HCV-2 subtypes circulating in the Tunisian population confirms the great diversity of HCV-2 viruses and increases the total number of HCV-2 subtypes from 21 to 23.Peer Reviewe

First case of childhood Takayasu arteritis with renal artery aneurysms

Takayasu arteritis is a large vessel systemic granulomatous vasculitis characterized by stenosis or obliteration of large and medium sized arteries. It commonly involves elastic arteries such as the aorta and its main branches. Renal artery involvement is rare and has not been reported in a child. We report a 12-year-old boy with Takayasu arteritis who developed severe hypertension, proteinuria, microscopic hematuria and renal dysfunction. Conventional angiography demonstrated aneurysms of both renal arteries and multiple microaneurysms of the superior mesenteric artery. This case report illustrates that the children with Takayasu arteritis can develop renal involvement resulting in hematuria, proteinuria and even renal failure

Phylogenetic Analysis and Epidemic History of Hepatitis C Virus Genotype 2 in Tunisia, North Africa.

HCV genotype 2 (HCV-2) has a worldwide distribution with prevalence rates that vary from country to country. High genetic diversity and long-term endemicity were suggested in West African countries. A global dispersal of HCV-2 would have occurred during the 20th century, especially in European countries. In Tunisia, genotype 2 was the second prevalent genotype after genotype 1 and most isolates belong to subtypes 2c and 2k. In this study, phylogenetic analyses based on the NS5B genomic sequences of 113 Tunisian HCV isolates from subtypes 2c and 2k were carried out. A Bayesian coalescent-based framework was used to estimate the origin and the spread of these subtypes circulating in Tunisia. Phylogenetic analyses of HCV-2c sequences suggest the absence of country-specific or time-specific variants. In contrast, the phylogenetic grouping of HCV-2k sequences shows the existence of two major genetic clusters that may represent two distinct circulating variants. Coalescent analysis indicated a most recent common ancestor (tMRCA) of Tunisian HCV-2c around 1886 (1869-1902) before the introduction of HCV-2k in 1901 (1867-1931). Our findings suggest that the introduction of HCV-2c in Tunisia is possibly a result of population movements between Tunisia and European population following the French colonization

Bayesian Skyline Plots for Demographic Reconstruction using NS5B sequences.

<p>A) subtype 2c, B) subtype 2k; X-axis: Date in Years; Y-axis: Estimated effective number of infections; Bold Line: Mean Effective Number of viral population. Upper and lower Lines: Upper and Lower HPD95% (High Population Density) of Effective Number of viral population.</p

The timeline of HCV subtype 2c introduction in Tunisia.

<p>The timeline of HCV subtype 2c introduction in Tunisia.</p

Phylogenetic analysis of isolates from Subtype 2k.

<p>Phylogenetic analyses were performed using the Maximum Composite Likelihood method included in the MEGA package (version 5.1). The reliability of the phylogenetic constructions was estimated by bootstrap analysis with 1000 pseudo replicate data sets. The tree is based on the analysis of a 222-nucleotide long fragment in the NS5B region (nucleotides 8346 to 8568 according to the H77-1a prototype strain, AF009606). It includes the 11 studied Tunisian sequences (in red) and 39 HCV-2k field sequences from other countries (in black). All the sequences were indicated by their Accession Numbers followed by the country code and the collection date. The country codes according to the standard abbreviation are: France (FRA), Martinique (MTQ), Canada (CAN), Russia (RUS), United Kingdom (GBR), Uzbekistan (UZB), Azerbaijan (AZE), Morocco (MAR), Iran (IRN) and Moldova (MDA).</p

_tMRCA estimations using the NS5B region for the HCV- 2c and HCV-2k in Tunisia.

<p>_tMRCA estimations using the NS5B region for the HCV- 2c and HCV-2k in Tunisia.</p

Phylogenetic analysis of isolates from subtype 2c.

<p>Phylogenetic analyses were performed using the Maximum Composite Likelihood method included in the MEGA package (version 5.1). The reliability of the phylogenetic constructions was estimated by bootstrap analysis with 1000 pseudo replicate data sets. The tree is based on the analysis of a 222-nucleotide-long fragment in the NS5B region (nucleotides 8316 to 8537 according to the H77-1a prototype strain, AF009606). It includes the 102 studied Tunisian sequences (in red) and 53 HCV-2c field sequences from other countries (in black). All the sequences were indicated by their Accession Numbers followed by the country code and the collection date. The country codes according to the standard abbreviation are: France (FRA), Martinique (MTQ), Canada (CAN), Italy (ITA), Venezuela (VEN), Ghana (GHA), Russia (RUS), Netherlands (NLD), Spain (ESP), Japan (JPN), Germany (DEU), Argentina (ARG) and United Kingdom (GBR).</p