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SELECTBIO Conferences Extracellular Vesicles 2023: Technologies, Biomarker Cargo & Diagnostics

Fatah Kashanchi's Biography

Fatah Kashanchi, Professor and Director of Research, Lab of Molecular Virology, George Mason University

For the past eighteen years Kashanchi lab has been interested in understanding the mechanism of viral gene expression in human viruses and how the virus and the host control the dynamics of fundamental machineries needed for viral replication and/or host survival. They also have ample experience with biochemical pathways that leads to transcription and chromatin remolding using in vitro reconstituted machineries. These complexes with epigenetic modifications utilize host signaling events and therapeutic targets that control viral replication. In recent years, they have also started focusing on Extracellular vesicles (i.e., exosomes) mainly from latent virally infected cells. These cells remain in the body for a long period of time can be extended to the life of a person (i.e., CNS cells). These latent cells produce exosomes that carry markers of the infection including RNA and protein sequences specific to a given virus. The lab for the first time showed that viral release and exosome release have overlapping biogenesis in the ESCRT pathway. For instance, HIV-1 latent cells utilize ESCRT-I for viral release, and ESCRT-II for exosomal release. Using in vitro and in vivo (both patient samples and animal models), the lab has found that exosomes from HIV-1 infected cells carry short non-coding RNAs (i.e., TAR) which regulate TLR3 and other pathways in the recipient cells. Similar results were also observed from other neuro-tropic RNA viral infections including HTLV-1, Ebola, RVFV, SARS, and Zika infection.

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Cross Talk Between Viruses and EV Biogenesis

Wednesday, 26 July 2023 at 16:00

Add to Calendar ▼2023-07-26 16:00:002023-07-26 17:00:00Europe/LondonCross Talk Between Viruses and EV BiogenesisExtracellular Vesicles 2023: Technologies, Biomarker Cargo and Diagnostics in Orlando, FloridaOrlando,

Most RNA and DNA viruses package and release their products (DNA, RNA, proteins) in EVs to avoid detection by the host immune system. In the current study we have addressed two main questions related to timing of the EV vs. virus release using HIV-1 as a model system, and have further found a new method of isolating viral populations that have never been described before. To date, it is not clear whether there is a timing difference between EV and virion release from infected cells. Here, we found that EVs precede the secretion of viral particles at 6 hrs post-transcriptional activation and release. This early EV release could shed light on how the contents of EVs are able to increase the susceptibility of viral infection, perhaps by priming the environment prior to viral egress or altering the progression of the cell cycle in recipient cells. We also have found that when separating EVs using differential ultracentrifugation, size exclusion chromatography or simple size filtration, there are at least three distinct sizes and functional viruses when using HIV-1 as a model system.  Validation of the data was performed utilizing blocking infectivity with broadly neutralizing antibodies or culturing the producer cell lines in the presence of anti-retroviral drugs to interfere with the production of infectious virions.  Collectively, our results show how viruses use EV pathways to release their cargo prior to virion release and the virions are very heterogenous in size, biochemical and biophysical characteristics.

Add to Calendar ▼2023-07-26 00:00:002023-07-27 00:00:00Europe/LondonExtracellular Vesicles 2023: Technologies, Biomarker Cargo and DiagnosticsExtracellular Vesicles 2023: Technologies, Biomarker Cargo and Diagnostics in Orlando, FloridaOrlando,