Browsing by Subject "Virus Diseases"
Now showing 1 - 8 of 8
- Results Per Page
- Sort Options
Item Antiviral chemotherapy(1972-03-09) Luby, James P.Item Autophagy in Antiviral Immunity(2012-08-15) Orvedahl, Anthony Walter; Levine, BethAutophagy is an evolutionarily conserved pathway in which cytoplasmic material is sequestered in a double-membrane vesicle and delivered to the lysosome for degradation. During times of stress, autophagy functions to generate essential nutrients through the degradation of non-essential cytoplasmic contents. It is also the only known mechanism for removal of damaged or superfluous organelles and cytoplasmic contents that are too large to be degraded by the proteasome. Given the critical role for autophagy in stress response and in maintaining cell cytoplasmic quality control, it is not surprising that autophagy plays an essential role in the host response to infection, and that microbes have evolved mechanisms to counteract or evade autophagy. In this work, we studied the role of autophagy inhibition in a mouse model of herpes simplex virus type I (HSV-1) encephalitis, investigated the role of autophagy in protection against Sindbis virus infection of the central nervous system, and identified novel host genes involved in targeting viral proteins to the autophagy pathway. We found that the HSV-1 encoded neurovirulence protein ICP34.5 interacted with the host autophagy protein Beclin 1, and that this interaction was essential for HSV-1 neurovirulence. This was the first example of a viral virulence protein that targets host autophagy, and provided evidence that autophagy functions in innate immunity to viruses. In the second study, we found that the host autophagy gene Atg5 was required to protect against lethal Sindbis virus CNS diseases, and that autophagy targeted viral proteins for degradation in brains of infected mice and cells in vitro. We found that the autophagy adaptor protein p62 was involved in targeting viral proteins for autophagic degradation and this promoted survival of infected cells. This study demonstrated that clearance of viral proteins by autophagy was an important mechanism for cellular and organismal survival during viral infection. Lastly, we performed a genome-wide siRNA screen to identify novel host factors required for autophagic targeting of viral proteins. We identified previously unappreciated cellular networks and genes that were involved in targeting viral proteins for autophagy. One of these factors, SMURF1, is an E3 ubiquitin ligase that not only functions to target viral proteins, but is also involved in targeting damaged mitochondria for autophagic clearance.Item Discovery of Unique Antiviral Pathways in a Bat Viral Reservoir, the Black Flying Fox(2018-04-03) De La Cruz Rivera, Pamela Cristina; Alto, Neal; Schoggins, John W.; Pfeiffer, Julie K.; Russell, David W.Bats are asymptomatic reservoirs for a number of viral pathogens. How they manage to host highly pathogenic viruses such a Nipah and Marburg without showing clinical symptoms remains unclear. One of the earliest defenses vertebrates use to control viral infections is the interferon response. Upon viral infection, cells produce interferon which inhibits viral infection through downstream effectors called interferon stimulated genes. I questioned whether bat interferon stimulated genes contained unique properties that would make bats less susceptible to damage from viral infection. To address this, I used genetic tools to identify which interferon stimulated genes were expressed in cells from the black flying fox (Pteropus alecto). I found that RNASEL is uniquely induced in cells from the black flying fox, and that its activation is important for preventing viral infection. To determine if any bat interferon stimulated genes had evolved especially potent antiviral properties, I compared a group of bat and human interferon stimulated genes in a high-throughput format and discovered that bat IRF7 is more antiviral than human IRF7. Further studies demonstrated that bat IRF7 is active even in uninfected cells, and can induce a subset of protective antiviral genes without signaling through interferon. This function was in part due to unique serine residues at the C-terminal regulatory region of the protein that confer constitutive activity to bat IRF7. This work has uncovered two different mechanisms by which antiviral responses between bat and human hosts differ, and provides insight regarding how bats manage to keep numerous viral infections under control.Item [Southwestern News](2005-08-25) Siegfried, AmandaItem [Southwestern News](2003-06-09) Maier, ScottItem [UT Southwestern Medical Center News](2008-11-23) Piloto, ConnieItem [UT Southwestern Medical Center News](2011-10-19) Bolles, Debbie; Wormser, DeborahItem [UT Southwestern Medical Center News](2010-01-18) Rian, Russell