The VI4 Infection and Immunology Symposium https://www.vumc.org/viiii/symposium will be held at the Student Life Center with an excellent lineup of external speakers and two of our very own:
BTW, if post-docs and students would like a similar profile to that featured here for Jessica, please contact Kaleigh Johnson. She is responsible for the construction of these effective profiles, which are meant to increase your visibility and networking!
Friday, April 13, 2018 - 5th floor atrium MRB III Sponsored by the Division of Molecular Pathogenesis - 2nd Friday Happy Hour - Cassat, and Skaar labs will be hosting.
Friday, April 27, 2018 - The Division of Molecular Pathogenesis monthly faculty meeting. This will be a business meeting - 3pm, room A-5305 MCN
If you would like to contribute an article highlight, from your lab or the lab of a colleague within MP, please feel free to email us.
A total of 25 publications featuring commentaries, reviews and primary research have posted on NCBI from division faculty in March 2018. Two are featured here: One by Dr. Louise Rollins Smith, in Science and one by Jonathan Knowlton from the Dermody lab, in Nature Microbiology. Congratulations for these accomplishments and thank you for the commentary contributions below.
(1) Voyles et al., 2018 Science 359 (6383): 1517-1519
"Shifts in disease dynamics in a tropical amphibian assemblage are not due to pathogen attenuations"
The article is highlighted by Louise:
"These studies began as far back as 2004 when Doug Woodhams was a postdoc in my lab and traveled to Panama to sample antimicrobial skin peptides among amphibians there. Over several years, we captured peptides from populations of some species before disease hit, during epidemics, and when the pathogen moved into an enzootic phase.
We also contributed recent experiments to test the immunosuppressive activity of early isolates of the pathogen and more recent ones. The title of the paper is “Shifts in disease dynamics in a tropical amphibian assemblage are not due to pathogen attenuation”. Briefly, some amphibian species are recovering in Panama as the disease shifts to the enzootic phase, but by several measures the pathogen has not changed.
Authors from Vanderbilt are me, Laura Reinert, Shawna McLetchie (grad student), and F. Ann Sobell (an undergrad).
(2) Knowlton et al., 2018 Nature Microbiology 3; 481-493
"The TRiC chaperonin controls reovirus replication through outer capsid folding"
As intracellular parasites, viruses hijack components of the cell to accomplish each step in a replication cycle. For years our lab has been interested in identifying these host proteins and exploring the molecular mechanisms by which these proteins aid viral replication. We developed a two-step RNAi-based screen to identify host proteins required for late steps in the replication of mammalian reovirus. After completing the screen, we were struck by the identification of numerous subunits of the TRiC chaperonin as top candidates. TRiC is required for life and functions in the eukaryotic cytoplasm to fold a subset (~10%) of cellular proteins, most notably actin and tubulin. Based on the known function of TRiC, we hypothesized that this chaperonin engages in the folding or assembly of one or more of the viral polypeptides. A series of co-immunoprecipitation experiments profiling the TRiC interactome in infected cells revealed that TRiC specifically interacts with the reovirus σ3 major outer-capsid protein. We took advantage of the rabbit reticulocyte-based in vitro translation system and purified recombinant human TRiC to demonstrate that TRiC is necessary and sufficient to fold the σ3 protein into its native state. In addition, we discovered that TRiC folds σ3 into a conformation capable of assembling into the mature reovirus outer capsid. Finally, we discovered that homologous capsid components of evolutionary disparate Reoviridae viruses also form a complex with TRiC, pointing towards a conserved mechanism of capsid folding. This work establishes a new function for TRiC in viral replication and provides rationale for the development of TRiC inhibitors as potential broad-spectrum antiviral therapeutics.
Links to Knowlton et al and associated commentary:
10. A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope. Zhou T, Zheng A, Baxa U, Chuang GY, Georgiev IS, Kong R, O'Dell S, Shahzad-Ul-Hussan S, Shen CH, Tsybovsky Y, Bailer RT, Gift SK, Louder MK, McKee K, Rawi R, Stevenson CH, Stewart-Jones GBE, Taft JD, Waltari E, Yang Y, Zhang B, Shivatare SS, Shivatare VS, Lee CD, Wu CY; NISC Comparative Sequencing Program, Mullikin JC, Bewley CA, Burton DR, Polonis VR, Shapiro L, Wong CH, Mascola JR, Kwong PD, Wu X. Immunity. 2018 Mar 20;48(3):500-513.e6. doi: 10.1016/j.immuni.2018.02.013. Epub 2018 Mar 13.
