Avant-Garde Award for HIV/AIDS Research: Novel Approaches to Innate Immunity Against HIV-1 and Co-infection Viruses
: E. M. Poeschla
: NIH (NIDA)
Term of Grant: F
ive Years (04/01/2017 – 03/31/2022)
Total Funding: $3.9 Million.
What it’s about
: The project will take forward a novel mouse model in which transgenic expression of the RNA genome copying enzyme of a picornavirus (poliovirus, enterovirus D68, and rhinoviruses are in this family) causes life-long, very highly elevated yet surprisingly well-tolerated expression of many interferon-stimulated genes (ISGs). This stably reconfigured innate immune system strongly protects the mice against diverse and otherwise lethal RNA and DNA virus infections (and HIV-1 in corroborative human cell models). Mouse genetics showed it is mediated through the viral dsRNA sensor MDA5 and its downstream signaling adaptor MAVS. It also requires the type I IFN receptor. Crosses with RAG1 knockout mice, which have no mature functional T or B cells, show it does not at all require the adaptive, antigen-specific immune system. Central features differ intriguingly from other constitutive MDA5 or RIG-I activation states in animal models and humans, as there is no “interferonopathy,” other auto-inflammatory pathology (such as lupus), or indeed any apparent health or longevity cost. This basic research project will explore the fundamental basis for this sustained, healthy antiviral state and its potential application to protection against HIV-1 and co-infection viruses that afflict people suffering from addiction.
NIDA web link: https://www.drugabuse.gov/about-nida/organization/offices/office-nida-director-od/aids-research-program-arp/avant-garde-award-hivaids-research/nida-ava
Washington times article: http://www.washingtontimes.com/news/2017/apr/5/national-institute-on-drug-abuse-awards-three-scie/