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Our results suggest a link between nef gene functions and the progression rate in HIV-1-infected children. Moreover, non-progressor-associated variations in the core domain of Nef, together with the genetic analysis, suggest that nef gene evolution is shaped by an effective immune system in these patients.

BackgroundChikungunya virus is an emerging mosquito-borne pathogen with a wide global distribution. With the severe morbidity that it causes, chikungunya virus is a major public health problem in the affected areas and poses a considerable risk for unaffected areas hosting competent vector populations. In the summer of 2017, Italy experienced a chikungunya virus outbreak that spread in the Lazio region and caused a secondary outbreak in the Calabrian village of Guardavalle, with a final case number of 436. The causative strain was recognized as an Indian Ocean lineage (IOL) virus.MethodsTo understand the underlying genetic and molecular features of the outbreak virus, viruses from mosquito pools and clinical samples were isolated in cell culture and subjected to whole-genome sequencing and genetic analyses.ResultsAll 8 characterized genomes shared a high sequence identity. A distinct substitution pattern in the Italian 2017 viruses (including mutations in E1, E2, and nsP4) was partly shared with the Pakistani 2016 outbreak viruses. Evolutionary analyses indicate that these 2 recent outbreaks and several geographically widely distributed, travel-associated viruses form a cluster of rapidly emerging Indian-origin IOL viruses.ConclusionsOur analyses show that the 2017 Italian outbreak virus belongs to a cluster of novel IOL chikungunya viruses originating in India. Their emergence calls for enhanced monitoring and strengthened preparedness measures, including vector control programs and raised awareness among general practitioners in countries potentially at risk.

We analyzed hepatitis C virus (HCV) genotype 4 isolates circulating in the Alexandria District (Egypt) in terms of genetic divergence and the presence of different subtypes. Hypervariable region 1 (HVR1) and the NH2 region of the E2 protein were characterized, and the heterogeneity of subtype 4a isolates was evaluated by analyzing epitope frequencies, immunoproteasome prediction, and possible glycosylation patterns. The heterogeneity of the nucleotide sequences was greater than that found in previous studies, which reported only subtype 4a. Subtype 4a was most common (78% of cases), yet four new subtypes were found, with subtype 4m representing 11% of the cases and the other three subtypes representing another 11%. Substantial heterogeneity was also found when the intrasubtype 4a sequences were analyzed. Differences in the probability of glycosylation and in the positions of the different sites were also observed. The analysis of the predicted cytotoxic-T-lymphocyte epitopes showed differences in both the potential proteosome cleavage and the prediction score. The Egyptian isolates in our study also showed high variability in terms of the HVR1 neutralization epitope. Five of these isolates showed amino acid substitutions never previously observed (a total of six positions). Four of these residues (in four different isolates) were in positions involved in anchoring to the E2 glycoprotein core and in maintaining the HVR1 conformation. The results of this study indicate that HCV genotype 4 in Egypt is extremely variable, not only in terms of sequence, but also in terms of functional and immunological determinants. These data should be taken into account in planning the development of vaccine trials in Egypt.Hepatitis C virus (HCV) is the major etiological agent of chronic hepatitis and liver disease worldwide, and it is a major cause of morbidity and mortality. In 80% of cases, infection with HCV results in chronic hepatitis, possibly leading to cirrhosis and hepatocellular carcinoma (11,28).HCV is characterized by a high degree of nucleotide sequence variability. Overall, the heterogeneity of the viral genome ranges from 30 to 35% between different genotypes, although it varies with the specific region of the genome, and it has been used to define three types of regions: highly conserved regions (e.g., the 5Ј untranslated region), variable regions (e.g., envelope 1 [E1] and nonstructural 5b [NS5b]), and hypervariable regions (HVR) (e.g., HVR1 and HVR2 in E2) (48). Furthermore, because of errors of the RNA-dependent RNA polymerase, HCV has a high rate of mutation during replication, and it exists in the bloodstreams of infected persons as complex distributions of mutants known as viral quasispecies, which fluctuate during the course of the disease, mainly as a result of immune pressure (47,51,54). These coexisting mutant genomes always have a consensus, or master, sequence. In general, despite the potentially high mutation rate and variability of RNA viruses, changes in the consensus sequence of a viral population ...

HCV is a ssRNA virus belonging to the Flaviviruses and is found worldwide worldwide in humans. Following primary infection, persistent infection develops in more than 85% of cases, which in up to 30% of cases, may progress to liver disease, cirrhosis and hepatocellular carcinoma. The virus presents a high degree of genetic variability owing to the combination of a lack of proofreading by the RNA-dependent RNA polymerase and a high level of viral replication. This genetic variability allows the classification of genotypes, subtypes, isolates and quasispecies to which epidemiological and pathogenetic significance may be associated. The features and biological implications of HCV variability and of quasispecies dynamics in infection transmission, mechanisms of chronicity and resistance to antiviral therapy are discussed.