RESUMEN
Human adenovirus type 3 (HAdV-3) encompasses 15-87% of all adenoviral respiratory infections. The significant morbidity and mortality, especially among the neonates and immunosuppressed patients, demand the need for a vaccine or a targeted antiviral against this type. However, due to the existence of multiple hexon variants (3Hv-1 to 3Hv-25), the selection of vaccine strains of HAdV-3 is challenging. This study was designed to evaluate HAdV-3 hexon variants for the selection of potential vaccine candidates and the use of hexon gene as a target for designing siRNA that can be used as a therapy. Based on the data of worldwide distribution, duration of circulation, co-circulation and their percentage among all the variants, 3Hv-1 to 3Hv-4 were categorized as the major hexon variants. Phylogenetic analysis and the percentage of homology in the hypervariable regions followed by multi-sequence alignment, zPicture analysis and restriction enzyme analysis were carried out. In the phylogram, the variants were arranged in different clusters. The HVR encoding regions of hexon of 3Hv-1 to 3Hv-4 showed 16 point mutations resulting in 12 amino acids substitutions. The homology in HVRs was 81.81-100%. Therefore, the major hexon variants are substantially different from each other which justifies their inclusion as the potential vaccine candidates. Interestingly, despite the significant differences in the DNA sequence, there were many conserved areas in the HVRs, and we have designed functional siRNAs form those locations. We have also designed immunogenic vaccine peptide epitopes from the hexon protein using bioinformatics prediction tool. We hope that our developed siRNAs and immunogenic vaccine peptide epitopes could be used in the future development of siRNA-based therapy and designing a vaccine against HAdV-3.
Asunto(s)
Infecciones por Adenovirus Humanos/inmunología , Infecciones por Adenovirus Humanos/virología , Adenovirus Humanos/genética , Adenovirus Humanos/inmunología , Proteínas de la Cápside/genética , Proteínas de la Cápside/inmunología , ARN Interferente Pequeño/uso terapéutico , Infecciones por Adenovirus Humanos/prevención & control , Infecciones por Adenovirus Humanos/terapia , Sustitución de Aminoácidos , Anticuerpos Neutralizantes/inmunología , Proteínas de la Cápside/química , Biología Computacional , Simulación por Computador , Epítopos/inmunología , Humanos , Filogenia , Mutación Puntual , Unión Proteica , ARN Interferente Pequeño/química , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/prevención & control , Infecciones del Sistema Respiratorio/terapia , Infecciones del Sistema Respiratorio/virología , Análisis de Secuencia de Proteína , Vacunas Virales/genética , Vacunas Virales/inmunología , Replicación Viral/efectos de los fármacosRESUMEN
Recently, human adenovirus type 3 (HAdV-3) has become the most isolated HAdV worldwide. Restriction endonuclease analysis of globally isolated strains of HAdV-3 has uncovered 51 genome types to date. Information on the genome type is important to the epidemiological study of HAdV-3. In this study, analysis of 75 isolates of HAdV- 3 collected over a 24-year period in Fukui revealed: (1) the emergence of three novel genome types (HAdV-3a52, HAdV-3a53 and HAdV-3a54) and two known genome types (HAdV-3a and HAdV-3a54); (2) the spectrum of diseases caused by individual genome types and their major involvement in the paediatric age population; and (3) the co-circulation and replacement of genome types as a usual phenomenon. The rising number of HAdV-3 genome types indicates that the genetic variation of HAdV-3 is more than other HAdVs. Considering the clinical importance of HAdV-3 infection, its genetic diversity underscores the need for its continuous surveillance and genetic characterization.