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Full-Text Articles in Life Sciences

Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman Jul 2019

Iiv-6 Inhibits Nf-Kappab Responses In Drosophila, Cara C. West, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, Neal S. Silverman

Neal Silverman

The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-kappaB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur …


Leishmania Amazonensis Engages Cd36 To Drive Parasitophorous Vacuole Maturation, Kendi Okuda, Mei Tong, Brian Dempsey, Kathryn J. Moore, Ricardo T. Gazzinelli, Neal S. Silverman Sep 2016

Leishmania Amazonensis Engages Cd36 To Drive Parasitophorous Vacuole Maturation, Kendi Okuda, Mei Tong, Brian Dempsey, Kathryn J. Moore, Ricardo T. Gazzinelli, Neal S. Silverman

Neal Silverman

Leishmania amastigotes manipulate the activity of macrophages to favor their own success. However, very little is known about the role of innate recognition and signaling triggered by amastigotes in this host-parasite interaction. In this work we developed a new infection model in adult Drosophila to take advantage of its superior genetic resources to identify novel host factors limiting Leishmania amazonensis infection. The model is based on the capacity of macrophage-like cells, plasmatocytes, to phagocytose and control the proliferation of parasites injected into adult flies. Using this model, we screened a collection of RNAi-expressing flies for anti-Leishmania defense factors. Notably, we …


A Single Vertebrate Dna Virus Protein Disarms Invertebrate Immunity To Rna Virus Infection, Don B. Gammon, Sophie Duraffour, Daniel K. Rozelle, Heidi Hehnly, Rita Sharma, Michael E. Sparks, Cara C. West, Ying Chen, James J. Moresco, Graciela Andrei, John H. Connor, Darryl Conte Jr., Dawn E. Gundersen-Rindal, William L. Marshall, John R. Yates, Neal S. Silverman, Craig C. Mello Dec 2014

A Single Vertebrate Dna Virus Protein Disarms Invertebrate Immunity To Rna Virus Infection, Don B. Gammon, Sophie Duraffour, Daniel K. Rozelle, Heidi Hehnly, Rita Sharma, Michael E. Sparks, Cara C. West, Ying Chen, James J. Moresco, Graciela Andrei, John H. Connor, Darryl Conte Jr., Dawn E. Gundersen-Rindal, William L. Marshall, John R. Yates, Neal S. Silverman, Craig C. Mello

Neal Silverman

Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-kappaB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells …


Caspase-8 And Rip Kinases Regulate Bacteria-Induced Innate Immune Responses And Cell Death, Dan Weng, Robyn Lynn Marty-Roix, Sandhya Ganesan, Megan K. Proulx, Gregory I. Vladimer, William J. Kaiser, Edward S. Mocarski, Kimberly Lea Pouliot, Francis Ka-Ming Chan, Michelle A. Kelliher, Phillip A. Harris, John Bertin, Peter J. Gough, Dmitry M. Shayakhmetov, Jon D. Goguen, Katherine A. Fitzgerald, Neal S. Silverman, Egil Lien Jun 2014

Caspase-8 And Rip Kinases Regulate Bacteria-Induced Innate Immune Responses And Cell Death, Dan Weng, Robyn Lynn Marty-Roix, Sandhya Ganesan, Megan K. Proulx, Gregory I. Vladimer, William J. Kaiser, Edward S. Mocarski, Kimberly Lea Pouliot, Francis Ka-Ming Chan, Michelle A. Kelliher, Phillip A. Harris, John Bertin, Peter J. Gough, Dmitry M. Shayakhmetov, Jon D. Goguen, Katherine A. Fitzgerald, Neal S. Silverman, Egil Lien

Neal Silverman

A number of pathogens cause host cell death upon infection, and Yersinia pestis, infamous for its role in large pandemics such as the "Black Death" in medieval Europe, induces considerable cytotoxicity. The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF. Caspase-8 is known to mediate apoptotic death in response to infection with several viruses and to regulate programmed necrosis (necroptosis), but its role in bacterially induced cell death is poorly understood. Here we provide genetic …


Nf-Kappab Signaling Pathways In Mammalian And Insect Innate Immunity, Neal S. Silverman, Tom Maniatis Dec 2009

Nf-Kappab Signaling Pathways In Mammalian And Insect Innate Immunity, Neal S. Silverman, Tom Maniatis

Neal Silverman

In this review, we discuss recent advances in understanding the signaling pathways in mammalian and Drosophila innate immunity, with emphasis on the mechanisms by which NF-kappaB/Rel family proteins are activated.