Respiratory infections can be severe—even deadly—in some individuals, but not in others. Scientists at St. Jude Children's Research Hospital, the Peter Doherty Institute for Infection and Immunity and other collaborators have gained new understanding of why this is the case by uncovering an early molecular driver that underpins fatal disease.
Oleoyl-ACP-hydrolase (OLAH) is an enzyme involved in fatty acid metabolism. A new study, in , shows that OLAH drives severe disease outcomes. The important role of OLAH in has gone unrecognized for several reasons, including a lack of noticeable expression in healthy tissue, as well as the difficulty of obtaining datasets reflecting OLAH expression before and after infection.
In this study, the researchers pieced together years of collaborative projects spanning multiple diseases to create the comprehensive datasets needed to understand how OLAH works. "OLAH directly impacts disease severity in multiple globally relevant but distinct viral infections," said co-first and co-corresponding author Jeremy Chase Crawford, Ph.D.
, St. Jude Department of Host-Microbe Interactions. "We started with the very specific disease context of avian influenza, but by forming these collaborations we were able to interrogate substantially broader disease contexts for this biological mechanism.
" Transcriptomics reveals pivotal role of OLAH The first clues pointing toward OLAH as a driver of lethal disease came from studies of avian A(H7N9) influenza. Tran.