Illuminating (HTLV-1)-induced adult T-cell leukemia/lymphoma transcriptomic signature: A systems virology approach.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a poor prognosis malignancy of peripheral T-cells caused by human T-cell leukemia virus type 1 (HTLV-1). The low survival rates observed in the patients are the result of the lack of sufficient knowledge about the disease pathogenesis. METHODS: In the present study, we first identified differentially expressed genes in ATLL patients and the cellular signaling pathways affected by them. Then, genes of these pathways were subjected to more comprehensive evaluations, including WGCNA and module validation studies on five external datasets. Finally, potential biomarkers were selected for qRT-PCR validation. RESULTS: Thirteen signaling pathways, including Apoptosis, Human T-cell leukemia virus 1 infection, IL-17 signaling pathway, pathways in cancer, T cell receptor signaling pathway, Th1 and Th2 cell differentiation, and seven others were selected for deeper investigations. Results of our in-depth bioinformatics evaluations, highlighted pathways related to regulation of immune responses, T-cell receptor and activation, regulation of cell signaling receptors and messengers, Wnt signaling pathway, and apoptosis as key players in ATLL pathogenesis. MAPK3, PIK3CD, KRAS, NFKB1, TNF, PLCB3, PLCB2, PLCB1, MAPK11, JUN, ITPR1, ADCY1, GNAQ, ADCY3, ADCY4, CHEK1, CCND1, SOS2, BAX, FOS and GNA12 were identified as possible biomarkers. Upregulation of ADCY1 and ADCY3 genes was confirmed via qRT-PCR. CONCLUSIONS: In this study, we performed a deep bioinformatic examination on a limited set of genes with high probabilities of involvement in the pathogenesis of ATLL. Our results highlighted signaling pathways and genes with potential key roles in disease formation and resistance against current treatment strategies. Further studies are required to test the possible benefits of highlighted genes as biomarkers and targets of treatment.

Genomic characterization and phylogenetic evolution of the canine parvoviruses in Iranian dogs, a nationwide study: CPV evolutionary analysis in Iran.

Canine Parvo Virus 2 (CPV-2) culminated in lots of fatalities in domestic dogs since its emergence in 1978. Mainly, it is responsible for severe hemorrhagic diarrhea, vomiting, and dehydration. CPV-2 has three main variants known as 2a, 2b, and 2c. Due to the necessity of monitoring the evolutionary parameters of the virus, and also the lack of comprehensive study of CPV2 in Iran, this study is done for the first time in this country not only to characterize Iranian CPV genomes but also to study the evolutionary parameters and phylodynamics of CPV. The phylogenetic trees were constructed using the Maximum Likelihood (ML) method. By the use of the Bayesian Monte Carlo Markov Chain (BMCMC) method, evolutionary analysis and phylodynamics of the virus were investigated. Phylogenetic results showed that all Iranian isolates were classified in the CPV-2a variant. The central part of Iran was suggested to be the origin of the virus, especially the Alborz province. Before its prevalence throughout the country, the virus circulated in the central part, in Thran, Karaj, and Qom. Mutational analysis showed a positive selection pressure of CPV-2a. Investigating the evolutionary parameters of the virus proposed 1970 to be the date of birth of the virus, with a 95% credible interval between 1953 and 1987. The effective number of infections increased dramatically from 2012 to 2015, then faced a slightly decreasing trend from 2015 to 2019. A considerable up warding pattern was witnessed from the middle of 2019, which can be taken as a concern about the risk of vaccination failure.