BackgroundThe HIV-1 spread in the Middle East and North Africa (MENA) has not been previously characterised using the phylogenetic approach. The aim of the current study was to investigate the genetic diversity and domestic transmission of HIV-1 in the MENA.MethodsA total of 2036 HIV-1 sequences available in Genbank and collected in the MENA during 1988–2016 were used together with 715 HIV-1 reference sequences that were retrieved from Genbank based on genetic similarity with the MENA sequences. The REGA and COMET tools were used to determine HIV-1 subtypes and circulating recombinant forms. Maximum Likelihood and Bayesian phylogenetic analyses were used to identify and date HIV-1 transmission clusters.ResultsAt least 21 HIV-1 subtypes and recombinant forms were prevalent in the MENA. Subtype B was the most common variant (39%), followed by CRF35_AD (19%) and CRF02_AG (14%). The most common genetic region was pol, and 675 partial pol sequences (average of 1005 bp) were eligible for detailed phylogenetic analysis. Fifty-four percent of the MENA sequences formed HIV-1 transmission clusters. Whereas numerous clusters were country-specific, some clusters indicated transmission links between countries for subtypes B, C and CRF02_AG. This was more common in North Africa compared with the Middle East (p < 0.001). Recombinant forms had a larger proportion of clustering compared to pure subtypes (p < 0.001). The largest MENA clusters dated back to 1991 (an Algerian CRF06_cpx cluster of 43 sequences) and 2002 (a Tunisian CRF02_AG cluster of 48 sequences).ConclusionsWe found an extensive HIV-1 diversity in the MENA and a high proportion of sequences in transmission clusters. This study highlights the need for preventive measures in the MENA to limit HIV-1 spread in this region.
There is increasing evidence that hepatitis B virus (HBV) infections with different genotypes and subgenotypes differ in response to treatment and long-term prognosis. The differences emerge from variability within the genomes that leads to structural deviations at the pregenomic level and to changes at the translational level. Naturally occurring HBV strains covering the four major genotypes A-D were obtained from 393 patients and part of the genome was amplified using polymerase chain reaction (PCR), sequenced, and analyzed for mutational differences in the precore and core promoter regions. The study confirmed that core promoter and precore mutations occur at key positions (A1762T, G1764A, G1896A, and G1899A), and that the proportions of strains with seroconvertion in patients differ between the four HBV genotypes. A rare double mutation (C1857T together with G1897A) was observed, and C1856T was found together with the emerging G1898A mutation, which itself was found to be more widespread geographically than previously described. We found a novel mutation (T1850C), never before observed in human HBV strains but known from woodchuck hepatitis virus (WHV). A novel association of mutation C1773T with G1764T, C1766A, and G1757A was also found within a site already suggested to be a putative binding site for HNF-3. This novel association is proposed by us to be of importance for additional binding of HNH-2 to this site and is a better indicator of the emergence of the double mutation G1764T and C1766A than the G1757A mutation proposed previously.
Chronic carriers of hepatitis B infection often harbour virus strains with mutations in the precore region. These mutations are temporally associated with the development of HBeAg loss and seroconversion to anti-HBe. The most common precore mutation is a stop codon at position 1896, but other mutations leading to abolished HBeAg secretion have been described. Here, a novel precore mutation introducing a lysine in the precore position 28, a sequence shared by non-human primates but not by other human isolates, is described. However, the insertion causes a frame-shift preventing the expression of HBeAg by introducing a stop codon 5 aa downstream of the mutation. Analysis of the predicted RNA secondary structure indicates that the insertion could occur without fatally affecting the stability of the stem-loop encapsidation signal.
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