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.

The Worldwide Prevalence of Herpes Simplex Virus Encephalitis and Meningitis: A Systematic Review and Meta-Analysis.

Given the relatively high frequency of central nervous system infections and considerable mor- tality and morbidity reported to be caused by herpes simplex viruses among the other viral agents, having a clear knowledge about their epidemiological profile seems necessary. This systematic review and meta-analysis aimed to determine the relative frequency and preva- lence of herpes simplex encephalitis and meningitis in patients tested for viral etiologies. A comprehensive systematic review was performed in PubMed, Scopus, and Web of Science databases, searching for studies on the prevalence and relative frequency of herpes sim- plex virus 1 and herpes simplex virus 2 encephalitis and meningitis. Seventy-one studies were included. Overall, the prevalence of herpes simplex virus encephalitis among patients tested was 8% (95% confidence interval, 6%-11%; I2 = 98%) and the prevalence of herpes simplex virus meningitis among aseptic patients tested was 4% (95% confidence interval, 3%-7%; I2 = 95%), and a significant difference was observed by region. The results of our subgroup analysis for herpes simplex virus encephalitis revealed a prevalence of 8% for pediatric patients and ado- lescents and 12% for adults. The results for herpes simplex virus meningitis showed a prevalence of 4% for pediatric patients and adolescents and 9% for adults. We observed significant differ- ences in the frequency of herpes simplex virus 1 and herpes simplex virus 2 detection rates by region. Having high rates of missed cases due to inadequate, highly sensitive paraclinical tests performed on patients with suspected viral central nervous system infection is one of the pos- sible factors. More studies are needed to detect the possible flaws in the process of diagnosis in different regions.

Identification of novel miRNAs potentially involved in the pathogenesis of adult T-cell leukemia/lymphoma using WGCNA followed by RT-qPCR test of hub genes.

BACKGROUND: Adult T-cell Lymphoma/Leukemia (ATLL) is characterized by the malignant proliferation of T-cells in Human T-Lymphotropic Virus Type 1 and a high mortality rate. Considering the emerging roles of microRNAs (miRNAs) in various malignancies, the analysis of high-throughput miRNA data employing computational algorithms helps to identify potential biomarkers. METHODS: Weighted gene co-expression network analysis was utilized to analyze miRNA microarray data from ATLL and healthy uninfected samples. To identify miRNAs involved in the progression of ATLL, module preservation analysis was used. Subsequently, based on the target genes of the identified miRNAs, the STRING database was employed to construct protein-protein interaction networks (PPIN). Real-time quantitative PCR was also performed to validate the expression of identified hub genes in the PPIN network. RESULTS: After constructing co-expression modules and then performing module preservation analysis, four out of 15 modules were determined as ATLL-specific modules. Next, the hub miRNA including hsa-miR-18a-3p, has-miR-187-5p, hsa-miR-196a-3p, and hsa-miR-346 were found as hub miRNAs. The protein-protein interaction networks were constructed for the target genes of each hub miRNA and hub genes were identified. Among them, UBB, RPS15A, and KMT2D were validated by Reverse-transcriptase PCR in ATLL patients. CONCLUSION: The results of the network analysis of miRNAs and their target genes revealed the major players in the pathogenesis of ATLL. Further studies are required to confirm the role of these molecular factors and to discover their potential benefits as treatment targets and diagnostic biomarkers.