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Articles 1 - 10 of 10
Full-Text Articles in Medicine and Health Sciences
Synergy Of Two Low-Affinity Nlss Determines The High Avidity Of Influenza A Virus Nucleoprotein Np For Human Importin Α Isoforms., Wei Wu, Rajeshwer S. Sankhala, Tyler J Florio, Lixin Zhou, Nhan L.T. Nguyen, Ravi K. Lokareddy, Gino Cingolani, Nelly Panté
Synergy Of Two Low-Affinity Nlss Determines The High Avidity Of Influenza A Virus Nucleoprotein Np For Human Importin Α Isoforms., Wei Wu, Rajeshwer S. Sankhala, Tyler J Florio, Lixin Zhou, Nhan L.T. Nguyen, Ravi K. Lokareddy, Gino Cingolani, Nelly Panté
Department of Biochemistry and Molecular Biology Faculty Papers
The influenza A virus nucleoprotein (NP) is an essential multifunctional protein that encapsidates the viral genome and functions as an adapter between the virus and the host cell machinery. NPs from all strains of influenza A viruses contain two nuclear localization signals (NLSs): a well-studied monopartite NLS1 and a less-characterized NLS2, thought to be bipartite. Through site-directed mutagenesis and functional analysis, we found that NLS2 is also monopartite and is indispensable for viral infection. Atomic structures of importin α bound to two variants of NLS2 revealed NLS2 primarily binds the major-NLS binding site of importin α, unlike NLS1 that associates …
Taking Control: Reorganization Of The Host Cytoskeleton By Chlamydia., Jordan Wesolowski, Fabienne Paumet
Taking Control: Reorganization Of The Host Cytoskeleton By Chlamydia., Jordan Wesolowski, Fabienne Paumet
Department of Microbiology and Immunology Faculty Papers
Both actin and microtubules are major cytoskeletal elements in eukaryotic cells that participate in many cellular processes, including cell division and motility, vesicle and organelle movement, and the maintenance of cell shape. Inside its host cell, the human pathogen Chlamydia trachomatis manipulates the cytoskeleton to promote its survival and enhance its pathogenicity. In particular, Chlamydia induces the drastic rearrangement of both actin and microtubules, which is vital for its entry, inclusion structure and development, and host cell exit. As significant progress in Chlamydia genetics has greatly enhanced our understanding of how this pathogen co-opts the host cytoskeleton, we will discuss …
Differentiation And Protective Capacity Of Virus-Specific Cd8, Vesselin T. Tomov, Olesya Palko, Chi Wai Lau, Ajinkya Pattekar, Yuhang Sun, Ralitza Tacheva, Bertram Bengsch, Sasikanth Manne, Gabriela L. Cosma, Laurence C. Eisenlohr, Timothy J. Nice, Herbert W. Virgin, E. John Wherry
Differentiation And Protective Capacity Of Virus-Specific Cd8, Vesselin T. Tomov, Olesya Palko, Chi Wai Lau, Ajinkya Pattekar, Yuhang Sun, Ralitza Tacheva, Bertram Bengsch, Sasikanth Manne, Gabriela L. Cosma, Laurence C. Eisenlohr, Timothy J. Nice, Herbert W. Virgin, E. John Wherry
Department of Microbiology and Immunology Faculty Papers
Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8+ T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8+ T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion. These MNV-specific Trm cells remained highly functional yet appeared ignorant of ongoing viral replication. Pre-existing MNV-specific Trm cells provided partial protection against chronic infection but largely ceased …
Stromal Cyclin D1 Promotes Heterotypic Immune Signaling And Breast Cancer Growth, Timothy G. Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R. Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Matthew C. Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P. Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas Craig Hooper, Zuoren Yu, Aaron R. Goldman, David W. Speicher, Lisa Laury-Kleintop, Richard G. Pestell
Stromal Cyclin D1 Promotes Heterotypic Immune Signaling And Breast Cancer Growth, Timothy G. Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R. Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Matthew C. Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P. Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas Craig Hooper, Zuoren Yu, Aaron R. Goldman, David W. Speicher, Lisa Laury-Kleintop, Richard G. Pestell
Department of Cancer Biology Faculty Papers
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased > 30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1Stroma) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy. Cyclin D1Stroma had profound effects on the breast tumor microenvironment increasing the recruitment of F4/80+ and CD11b+ macrophages and increasing …
April:Taci Axis Is Dispensable For The Immune Response To Rabies Vaccination., Shannon L. Haley, Evgeni P. Tzvetkov, Andrew G. Lytle, Kishore R. Alugupalli, Joseph R. Plummer, James P. Mcgettigan
April:Taci Axis Is Dispensable For The Immune Response To Rabies Vaccination., Shannon L. Haley, Evgeni P. Tzvetkov, Andrew G. Lytle, Kishore R. Alugupalli, Joseph R. Plummer, James P. Mcgettigan
Department of Microbiology and Immunology Faculty Papers
There is significant need to develop a single-dose rabies vaccine to replace the current multi-dose rabies vaccine regimen and eliminate the requirement for rabies immune globulin in post-exposure settings. To accomplish this goal, rabies virus (RABV)-based vaccines must rapidly activate B cells to secrete antibodies which neutralize pathogenic RABV before it enters the CNS. Increased understanding of how B cells effectively respond to RABV-based vaccines may improve efforts to simplify post-exposure prophylaxis (PEP) regimens. Several studies have successfully employed the TNF family cytokine a proliferation-inducing ligand (APRIL) as a vaccine adjuvant. APRIL binds to the receptors TACI and B cell …
Metabolite Profiling Of Infection-Associated Metabolic Markers Of Onchocerciasis., Sasisekhar Bennuru, Sara Lustigman, David Abraham, Thomas B. Nutman
Metabolite Profiling Of Infection-Associated Metabolic Markers Of Onchocerciasis., Sasisekhar Bennuru, Sara Lustigman, David Abraham, Thomas B. Nutman
Department of Microbiology and Immunology Faculty Papers
The global efforts for onchocerciasis elimination may require additional tools (safe micro and macrofilaricidal drugs, vaccines and biomarkers) as elimination efforts move toward the "end game". Efforts toward the identification of suitable biomarkers have focused on specific protein(s) and/or nucleic acids, but metabolites present an alternative option as they have limited half-lives and are the result of combinatorial effects. In comparison to previously used methodology of LC-MS for metabolomic approaches, we used a non-targeted capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) to analyze the serum metabolic profiles of Ov-infected and -uninfected individuals (n=20). We identified 286 known metabolites (167 in the …
The 11s Proteasomal Activator Regγ Impacts Polyglutamine-Expanded Androgen Receptor Aggregation And Motor Neuron Viability Through Distinct Mechanisms., Jill M. Yersak, Heather L. Montie, Erica S. Chevalier-Larsen, Yuhong Liu, Lan Huang, Martin Rechsteiner, Diane E. Merry
The 11s Proteasomal Activator Regγ Impacts Polyglutamine-Expanded Androgen Receptor Aggregation And Motor Neuron Viability Through Distinct Mechanisms., Jill M. Yersak, Heather L. Montie, Erica S. Chevalier-Larsen, Yuhong Liu, Lan Huang, Martin Rechsteiner, Diane E. Merry
Department of Biochemistry and Molecular Biology Faculty Papers
Spinal and bulbar muscular atrophy (SBMA) is caused by expression of a polyglutamine (polyQ)-expanded androgen receptor (AR). The inefficient nuclear proteasomal degradation of the mutant AR results in the formation of nuclear inclusions containing amino-terminal fragments of the mutant AR. PA28γ (also referred to as REGγ) is a nuclear 11S-proteasomal activator with limited proteasome activation capabilities compared to its cytoplasmic 11S (PA28α, PA28β) counterparts. To clarify the role of REGγ in polyQ-expanded AR metabolism, we carried out genetic and biochemical studies in cell models of SBMA. Overexpression of REGγ in a PC12 cell model of SBMA increased polyQ-expanded AR aggregation …
Chlamydia Hijacks Arf Gtpases To Coordinate Microtubule Posttranslational Modifications And Golgi Complex Positioning., Jordan Wesolowski, Mary M. Weber, Agata Nawrotek, Cheryl A. Dooley, Mike Calderon, Claudette M. St Croix, Ted Hackstadt, Jacqueline Cherfils, Fabienne Paumet
Chlamydia Hijacks Arf Gtpases To Coordinate Microtubule Posttranslational Modifications And Golgi Complex Positioning., Jordan Wesolowski, Mary M. Weber, Agata Nawrotek, Cheryl A. Dooley, Mike Calderon, Claudette M. St Croix, Ted Hackstadt, Jacqueline Cherfils, Fabienne Paumet
Department of Microbiology and Immunology Faculty Papers
The intracellular bacterium Chlamydia trachomatis develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both …
Chemical And Structural Characterization Of A Model Post-Termination Complex (Potc) For The Ribosome Recycling Reaction: Evidence For The Release Of The Mrna By Rrf And Ef-G., Nobuhiro Iwakura, Takeshi Yokoyama, Fabio Quaglia, Kaoru Mitsuoka, Kazuhiro Mio, Hideki Shigematsu, Mikako Shirouzu, Akira Kaji, Hideko Kaji
Chemical And Structural Characterization Of A Model Post-Termination Complex (Potc) For The Ribosome Recycling Reaction: Evidence For The Release Of The Mrna By Rrf And Ef-G., Nobuhiro Iwakura, Takeshi Yokoyama, Fabio Quaglia, Kaoru Mitsuoka, Kazuhiro Mio, Hideki Shigematsu, Mikako Shirouzu, Akira Kaji, Hideko Kaji
Department of Biochemistry and Molecular Biology Faculty Papers
A model Post-Termination Complex (PoTC) used for the discovery of Ribosome Recycling Factor (RRF) was purified and characterized by cryo-electron microscopic analysis and biochemical methods. We established that the model PoTC has mostly one tRNA, at the P/E or P/P position, together with one mRNA. The structural studies were supported by the biochemical measurement of bound tRNA and mRNA. Using this substrate, we establish that the release of tRNA, release of mRNA and splitting of ribosomal subunits occur during the recycling reaction. Order of these events is tRNA release first followed by mRNA release and splitting almost simultaneously. Moreover, we …
The Final (Oral Ebola) Vaccine Trial On Captive Chimpanzees?, Peter D. Walsh, Drishya Kurup, Dana L. Hasselschwert, Christoph Wirblich, Jason E. Goetzmann, Matthias J. Schnell
The Final (Oral Ebola) Vaccine Trial On Captive Chimpanzees?, Peter D. Walsh, Drishya Kurup, Dana L. Hasselschwert, Christoph Wirblich, Jason E. Goetzmann, Matthias J. Schnell
Department of Microbiology and Immunology Faculty Papers
Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV. Vaccination did not induce serious health complications. Blood chemistry, hematologic, and body mass correlates of psychological stress suggested …