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PLOS Studies on Anti-Viral Epigenetic Drugs, Liver Cancer Oncogene, Brazilian HIV Diversity

In PLOS Pathogens, a team from China describes an innate immune-related rise in anti-viral activity triggered with BRD4-inhibiting epigenetic drugs. Using a combination of fluorescent protein reporter assays and other experiments, the researchers assessed several chromatin-targeting drugs, demonstrating that they could dial down the activity of pseudorabies and other viruses by inhibiting BRD4 — an approach that appeared to prompt chromatin changes, DNA damage response mechanisms, and related innate immune responses. "Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases," they write.

Investigators in China present evidence that a microRNA called miR-520b targets a kinase enzyme encoded by the MLK3 gene, which has been implicated in oncogenesis in breast and other cancers in the past. As they report in PLOS One, the researchers used RT-PCR to track the expression of miR-520b in several liver cancer cell lines, following from prior reports describing decreased expression of the miRNA in an aggressive liver cancer line. Along with lower-than-usual miR-520b expression in the liver cancer cells, results from their follow-up reporter assay experiments suggested that the miRNA can target MLK3, while enhanced expression of that kinase appeared to boost liver cancer cells' migration potential. The authors suggest these and other findings from the study "support an oncogenic role of MLK3 in liver cancer."

Finally, a team from Brazil and Germany takes a look at viral genetic diversity in samples from Brazilian individuals with HIV experiencing virological failure, or failed HIV suppression, on antiretroviral therapy for another paper in PLOS One. Using targeted sequencing, phylogenetic analyses, and recombination analyses, the researchers assessed HIV-1 isolates from more than 600 individuals being treated with antiretroviral therapy in a state in northeastern Brazil, uncovering antiretroviral resistance in nearly three-quarters of the strains considered and an over-representation of strains from HIV subtype B, among other patterns. "Given the enormous HIV-1 diversity in Brazil," they write, "a better knowledge of its genetic variability is crucial for the understanding of inter-subtype recombination mechanisms, vaccine development, viral pathogenesis, transmission pathways, evaluation of antiretroviral drug resistance, and differentiation of therapeutic regimens."