Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 7 of 7

Full-Text Articles in Medicine and Health 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 …


Regulation Of The Drosophila Imd Pathway By Signaling Amyloids, Anni Kleino, Neal S. Silverman Jun 2019

Regulation Of The Drosophila Imd Pathway By Signaling Amyloids, Anni Kleino, Neal S. Silverman

Neal Silverman

Fruit flies elicit effective defense responses against numerous microbes. The responses against Gram-negative bacteria are mediated by the Imd pathway, an evolutionarily conserved NF-kappaB pathway recognizing meso-diaminopimelic acid (DAP)-type peptidoglycan from bacterial cell walls. Several reviews already provide a detailed view of ligand recognition and signal transduction during Imd signaling, but the formation and regulation of the signaling complex immediately downstream of the peptidoglycan-sensing receptors is still elusive. In this review, we focus on the formation of the Imd amyloidal signaling center and post-translational modifications in the assembly and disassembly of the Imd signaling complex.


Genomic Insights Into The Ixodes Scapularis Tick Vector Of Lyme Disease, Monika Gulia-Nuss,, Daniel R. Caffrey, Neal S. Silverman, Adam R. Wespiser, Catherine A. Hill Aug 2016

Genomic Insights Into The Ixodes Scapularis Tick Vector Of Lyme Disease, Monika Gulia-Nuss,, Daniel R. Caffrey, Neal S. Silverman, Adam R. Wespiser, Catherine A. Hill

Neal Silverman

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing approximately 57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, …


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 …


The Genome Of Anopheles Darlingi, The Main Neotropical Malaria Vector, Osvaldo Marinotti, Adam R. Wespiser, Daniel R. Caffrey, Douglas T. Golenbock, Neal S. Silverman Apr 2014

The Genome Of Anopheles Darlingi, The Main Neotropical Malaria Vector, Osvaldo Marinotti, Adam R. Wespiser, Daniel R. Caffrey, Douglas T. Golenbock, Neal S. Silverman

Neal Silverman

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors approximately 100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In …


Initial Multicenter Experience With Double Nucleoside Therapy For Human Immunodeficiency Virus Infection During Pregnancy, Neal S. Silverman, D. Heather Watts, Joseph Hitti, D. M. Money, E. Livingston, J. Axelrod, J. M. Ernest, Douglas Robbins, M. M. Divito Feb 2013

Initial Multicenter Experience With Double Nucleoside Therapy For Human Immunodeficiency Virus Infection During Pregnancy, Neal S. Silverman, D. Heather Watts, Joseph Hitti, D. M. Money, E. Livingston, J. Axelrod, J. M. Ernest, Douglas Robbins, M. M. Divito

Neal Silverman

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV …


Rudra Interrupts Receptor Signaling Complexes To Negatively Regulate The Imd Pathway, Kamna Aggarwal, Florentina Rus, Christie Vriesema-Magnuson, Deniz Erturk Hasdemir, Nicholas Paquette, Neal S. Silverman Dec 2009

Rudra Interrupts Receptor Signaling Complexes To Negatively Regulate The Imd Pathway, Kamna Aggarwal, Florentina Rus, Christie Vriesema-Magnuson, Deniz Erturk Hasdemir, Nicholas Paquette, Neal S. Silverman

Neal Silverman

Insects rely primarily on innate immune responses to fight pathogens. In Drosophila, antimicrobial peptides are key contributors to host defense. Antimicrobial peptide gene expression is regulated by the IMD and Toll pathways. Bacterial peptidoglycans trigger these pathways, through recognition by peptidoglycan recognition proteins (PGRPs). DAP-type peptidoglycan triggers the IMD pathway via PGRP-LC and PGRP-LE, while lysine-type peptidoglycan is an agonist for the Toll pathway through PGRP-SA and PGRP-SD. Recent work has shown that the intensity and duration of the immune responses initiating with these receptors is tightly regulated at multiple levels, by a series of negative regulators. Through two-hybrid screening …