Fatah Kashanchi, Professor, Laboratory of Molecular Virology, School of Systems Biology, and Lance Liotta, Co-Director, Applied Proteomics and Molecular Medicine, are working to mitigate virally driven HIV pathenogenesis in the central nervous system (CNS).
Preliminary data the researchers have gathered suggests that cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), may be effective in reducing HIV-1 transcription of both short, non-coding RNA such as trans-activating response (TAR) RNA, and full-length genomic RNA, thereby resulting in decreased production of virus.
The researchers have also found that the reduction in transcription results in a decreased incorporation of HIV-1 RNA into extracellular vesicles released from infected cells. This has been previously shown to contribute to dysfunction in recipient cells, including activation of the NF-kB pathway, a protein complex that controls transcription of DNA, cytokine production, and cell survival through TLR3 and increased susceptibility to infection. TLR3?is a member of the toll-like receptor family of pattern recognition receptors of the innate immune system.
The researchers hypothesize that cannabinoid treatment may affect host cell pathways, including autophagy and the endosomal sorting complexes required for transport (ESCRT) pathways, to alter EV release which can potentially mitigate EV-related dysfunction during viral infection of the CNS.
The researchers have two aims for their work.
First, they intend to define the mechanisms of cannabinoid-mediated decreased EV production and release in HIV-1 infected cells.
Second, they aim to determine the effect of CBD and THC on HIV-1 expression using 3D neurospheres. The overall positive impact of these two aims is to highlight the role of cannabinoids in EV release and dampening of the neuroinflammation.
The researchers will receive total funding of $450,000 from the U.S. Department of Health and Human Services for this research. Funding began in May 2020 and will conclude in late April 2022.