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.
Exosomes and Viruses: A Tale of Two Overlapping Worlds
Friday, 26 February 2021 at 08:00
Add to Calendar ▼2021-02-26 08:00:002021-02-26 09:00:00Europe/LondonExosomes and Viruses: A Tale of Two Overlapping WorldsExtracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and Therapeutics in Virtual ConferenceVirtual ConferenceSELECTBIOenquiries@selectbiosciences.com
Extracellular vesicles (EVs) play a significant role in intercellular communication by serving as a carrier for the transfer of membrane and cytosolic proteins, lipids, and RNA between cells. In recent years, using state of art technologies such as RNA seq, RPMA, and single cell omics, we have found that virally infected cells including HIV-1, HTLV-1, Rift Valley Fever, Zika, Ebola, and Coronavirus infected cells secret exosomes that contain biomarker of these infections in urine, saliva, CSF, and blood. We have been able to separate and characterize EVs from several different viruses including HIV-1. These EVs are not infectious and have a different density than infectious virions using gradients. They contain various viral RNAs including TAR (non-coding RNA), Nef, gp120/160 and Tat. The origin of these EVs are infected cells, especially when treated with cART or Interferons. They are present in patient samples tested (plasma and CSF, 33%-95%) to date (4 cohorts of 5-20 patients each). The EVs contribute to pro-inflammatory signals in the naïve recipient cells using TLR3 signaling. Recently, we have asked about the timing difference between EV and virus release from infected cells using serum starvation experiments from cells followed by release. Results from supernatants of uninfected cells showed a peak of tetraspanin proteins (CD63, CD81, and CD9) at 6 hours and a gradual decrease of all EV associated proteins by 24 hours. However, the EV from HIV-1 infected cells showed all three tetraspanins present at 3 hours and expression gradually increased up to 24 hours. HIV-1 viral proteins (p24, gp120, Nef) expression was present at 6 hours and continued to increase and peaked at 24 hours. HIV-1 supernatant 6- hour sample was found not to be infectious. However, infectious HIV-1 was successfully rescued from 24-hour sample.
Our data indicates that EV release may occur prior to viral release in infected cells, thereby implicating a potentially significant effect of EVs on uninfected recipient cells prior to subsequent viral infection.
Add to Calendar ▼2021-02-25 00:00:002021-02-26 00:00:00Europe/LondonExtracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and TherapeuticsExtracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and Therapeutics in Virtual ConferenceVirtual ConferenceSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2021-02-26 08:00:002021-02-26 09:00:00Europe/LondonExosomes and Viruses: A Tale of Two Overlapping WorldsExtracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and Therapeutics in Virtual ConferenceVirtual ConferenceSELECTBIOenquiries@selectbiosciences.com
