Study rewrites dogma of adenovirus an infection and double-stranded RNA

Challenging the dogma of what scientists thought they understood about DNA viruses, a group of researchers led by Children’s Hospital of Philadelphia (CHOP) has proven that adenovirus makes use of its personal environment friendly RNA splicing mechanisms to forestall the formation of double-stranded RNA, which in any other case would set off a number immune response. By splicing its RNA transcripts in a method that forestalls them from pairing with different viral messages, adenovirus evades host sensors that activate the immune system within the presence of double-stranded RNA. The findings have been printed at the moment as a “Breakthrough Article” in Nucleic Acids Research.

Prior to this work, researchers had assumed DNA viruses produced double-stranded RNA throughout an infection, on condition that transcription happens symmetrically on each prime and backside strands of viral DNA; most DNA viruses additionally encode proteins that inhibit host pathways that acknowledge double-stranded RNA as overseas. However, regardless of this assumption, there was no direct proof that DNA viruses just like the adenovirus produce double-stranded RNA.

To examine this concept, the analysis group, led by Matthew D. Weitzman, Ph.D., an investigator in CHOP’s Department of Pathology and Laboratory Medicine, and Alexander Price, Ph.D., a post-doctoral fellow within the Weitzman Laboratory, used imaging by microscopy with two unbiased monoclonal antibodies to ascertain whether or not adenovirus produces double-stranded RNA. To their shock, they discovered no detectable ranges of double-stranded RNA following adenovirus an infection. In distinction, they discovered considerable double-stranded RNA in cells contaminated with adenovirus mutants that have been faulty for viral RNA processing. When this occurred, host sensors for double-stranded RNA have been activated, launching the host immune system into motion.

“Through highly collaborative work, this study highlights a novel mechanism by which viruses can escape innate immune recognition by modulating host factors to promote efficient viral RNA production,” Weitzman mentioned. “Future research will need to account for this new discovery and investigate factors like small viral RNAs that were thought to block double-stranded RNA responses, but as these findings indicate, must exist for some other reason.”