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Pathogenic Microbiology Commons

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Articles 1 - 4 of 4

Full-Text Articles in Pathogenic Microbiology

Identification Of Zika Virus And Dengue Virus Dependency Factors Using Functional Genomics, George Savidis, William M. Mcdougall, Paul Meraner, Jill Perreira, Jocelyn M. Portmann, Gaia Trincucci, Sinu P. John, Aaron M. Aker, Nicholas Renzette, Douglas R. Robbins, Zhiru Guo, Sharone Green, Timothy F. Kowalik, Abraham L. Brass Jun 2016

Identification Of Zika Virus And Dengue Virus Dependency Factors Using Functional Genomics, George Savidis, William M. Mcdougall, Paul Meraner, Jill Perreira, Jocelyn M. Portmann, Gaia Trincucci, Sinu P. John, Aaron M. Aker, Nicholas Renzette, Douglas R. Robbins, Zhiru Guo, Sharone Green, Timothy F. Kowalik, Abraham L. Brass

Microbiology and Physiological Systems Publications and Presentations

The flaviviruses dengue virus (DENV) and Zika virus (ZIKV) are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of DENV and ZIKV, we completed orthologous functional genomic screens using RNAi and CRISPR/Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF), heparin sulfation (NDST1 and EXT1), and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC). We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systems-wide view of ...


The Ifitms Inhibit Zika Virus Replication, George Savidis, Jill Perreira, Jocelyn M. Portmann, Paul Meraner, Zhiru Guo, Sharone Green, Abraham L. Brass Jun 2016

The Ifitms Inhibit Zika Virus Replication, George Savidis, Jill Perreira, Jocelyn M. Portmann, Paul Meraner, Zhiru Guo, Sharone Green, Abraham L. Brass

Microbiology and Physiological Systems Publications and Presentations

Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses.


A Higher Activation Threshold Of Memory Cd8+ T Cells Has A Fitness Cost That Is Modified By Tcr Affinity During Tuberculosis, Stephen M. Carpenter, Claudio Nunes-Alves, Matthew G. Booty, Sing Sing Way, Samuel M. Behar Jan 2016

A Higher Activation Threshold Of Memory Cd8+ T Cells Has A Fitness Cost That Is Modified By Tcr Affinity During Tuberculosis, Stephen M. Carpenter, Claudio Nunes-Alves, Matthew G. Booty, Sing Sing Way, Samuel M. Behar

Microbiology and Physiological Systems Publications and Presentations

T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the ...


Human And Murine Clonal Cd8+ T Cell Expansions Arise During Tuberculosis Because Of Tcr Selection, Claudio Nunes-Alves, Matthew G. Booty, Stephen M. Carpenter, Alissa C. Rothchild, Constance J. Martin, Danielle Desjardins, Katherine Steblenko, Henrik N. Kløverpris, Rajhmun Madansein, Duran Ramsuran, Alasdair Leslie, Margarida Correia-Neves, Samuel M. Behar May 2015

Human And Murine Clonal Cd8+ T Cell Expansions Arise During Tuberculosis Because Of Tcr Selection, Claudio Nunes-Alves, Matthew G. Booty, Stephen M. Carpenter, Alissa C. Rothchild, Constance J. Martin, Danielle Desjardins, Katherine Steblenko, Henrik N. Kløverpris, Rajhmun Madansein, Duran Ramsuran, Alasdair Leslie, Margarida Correia-Neves, Samuel M. Behar

Microbiology and Physiological Systems Publications and Presentations

The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells ...