RESUMO
Baculoviruses are entomopathogens that carry large, double-stranded circular DNA genomes and infect insect larvae of Lepidoptera, Hymenoptera and Diptera, with applications in the biological control of agricultural pests, in the production of recombinant proteins and as viral vectors for various purposes in mammals. These viruses have a variable genetic composition that differs between species, with some sequences shared by all known members, and others that are lineage-specific or unique to isolates. Based on the analysis of nearly 300 sequenced genomes, a thorough bioinformatic investigation was conducted on all the baculoviral protein coding sequences, characterizing their orthology and phylogeny. This analysis confirmed the 38 protein coding sequences currently considered as core genes, while also identifying novel coding sequences as candidates to join this set. Accordingly, homology was found among all the major occlusion body proteins, thus proposing that the polyhedrin, granulin and CUN085 genes be considered as the 39th core gene of Baculoviridae.
Assuntos
Baculoviridae , Lepidópteros , Animais , Baculoviridae/genética , Proteínas Virais/genética , Proteínas Estruturais Virais , Insetos , MamíferosRESUMO
Baculoviruses are insect pathogens widely used as biotechnological tools in different fields of life sciences and technologies. The particular biology of these entities (biosafety viruses 1; large circular double-stranded DNA genomes, infective per se; generally of narrow host range on insect larvae; many of the latter being pests in agriculture) and the availability of molecular-biology procedures (e.g., genetic engineering to edit their genomes) and cellular resources (availability of cell lines that grow under in vitro culture conditions) have enabled the application of baculoviruses as active ingredients in pest control, as systems for the expression of recombinant proteins (Baculovirus Expression Vector Systems-BEVS) and as viral vectors for gene delivery in mammals or to display antigenic proteins (Baculoviruses applied on mammals-BacMam). Accordingly, BEVS and BacMam technologies have been introduced in academia because of their availability as commercial systems and ease of use and have also reached the human pharmaceutical industry, as incomparable tools in the development of biological products such as diagnostic kits, vaccines, protein therapies, and-though still in the conceptual stage involving animal models-gene therapies. Among all the baculovirus species, the Autographa californica multiple nucleopolyhedrovirus has been the most highly exploited in the above utilities for the human-biotechnology field. This review highlights the main achievements (in their different stages of development) of the use of BEVS and BacMam technologies for the generation of products for infectious and noninfectious human diseases. KEY POINTS: ⢠Baculoviruses can assist as biotechnological tools in human health problems. ⢠Vaccines and diagnosis reagents produced in the baculovirus platform are described. ⢠The use of recombinant baculovirus for gene therapy-based treatment is reviewed.
Assuntos
Baculoviridae , Vetores Genéticos , Animais , Baculoviridae/genética , Linhagem Celular , Humanos , Insetos , Proteínas Recombinantes/genéticaRESUMO
The adult mammalian cardiomyocyte has a very limited capacity to reenter the cell cycle and advance into mitosis. Therefore, diseases characterized by lost contractile tissue usually evolve into myocardial remodeling and heart failure. Analyzing the cardiac transcriptome at different developmental stages in a large mammal closer to the human than laboratory rodents may serve to disclose positive and negative cardiomyocyte cell cycle regulators potentially targetable to induce cardiac regeneration in the clinical setting. Thus we aimed at characterizing the transcriptomic profiles of the early fetal, late fetal, and adult sheep heart by employing RNA-seq technique and bioinformatic analysis to detect protein-encoding genes that in some of the stages were turned off, turned on, or differentially expressed. Genes earlier proposed as positive cell cycle regulators such as cyclin A, cdk2, meis2, meis3, and PCNA showed higher expression in fetal hearts and lower in AH, as expected. In contrast, genes previously proposed as cell cycle inhibitors, such as meis1, p16, and sav1, tended to be higher in fetal than in adult hearts, suggesting that these genes are involved in cell processes other than cell cycle regulation. Additionally, we described Gene Ontology (GO) enrichment of different sets of genes. GO analysis revealed that differentially expressed gene sets were mainly associated with metabolic and cellular processes. The cell cycle-related genes fam64a, cdc20, and cdk1, and the metabolism-related genes pitx and adipoq showed strong differential expression between fetal and adult hearts, thus being potent candidates to be targeted in human cardiac regeneration strategies.NEW & NOTEWORTHY We characterized the transcriptomic profiles of the fetal and adult sheep hearts employing RNAseq technique and bioinformatic analyses to provide sets of transcripts whose variation in expression level may link them to a specific role in cell cycle regulation. It is important to remark that this study was performed in a large mammal closer to humans than laboratory rodents. In consequence, the results can be used for further translational studies in cardiac regeneration.