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Michael J Conway, Berlin Londono-Renteria, Andrea Troupin, Alan M Watson, William B Klimstra, Erol Fikrig, Tonya M Colpitts
Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV) types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs) enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection...
September 2016: PLoS Neglected Tropical Diseases
Kellie Ann Jurado, Michael K Simoni, Zhonghua Tang, Ryuta Uraki, Jesse Hwang, Sarah Householder, Mingjie Wu, Brett D Lindenbach, Vikki M Abrahams, Seth Guller, Erol Fikrig
The strong association of Zika virus infection with congenital defects has led to questions of how a flavivirus is capable of crossing the placental barrier to reach the fetal brain. Here, we demonstrate permissive Zika virus infection of primary human placental macrophages, commonly referred to as Hofbauer cells, and placental villous fibroblasts. We also demonstrate Zika virus infection of Hofbauer cells within the context of the tissue ex vivo using term placental villous explants. In addition to amplifying infectious virus within a usually inaccessible area, the putative migratory activities of Hofbauer cells may aid in dissemination of Zika virus to the fetal brain...
August 18, 2016: JCI Insight
Laila Heringer, Brian J Johnson, Kara Fikrig, Bruna A Oliveira, Richard D Silva, Michael Townsend, Roberto Barrera, Álvaro E Eiras, Scott A Ritchie
The Gravid Aedes Trap (GAT) uses visual and olfactory cues to attract gravid Aedes aegypti (L.) that are then captured when knocked down by a residual pyrethroid surface spray. However, the use of surface sprays can be compromised by poor availability of the spray and pesticide resistance in the target mosquito. We investigated several "alternative" insecticide and insecticide-free killing agents for use in the GAT. This included long-lasting insecticide-impregnated nets (LLINs), vapor-active synthetic pyrethroids (metofluthrin), canola oil, and two types of dry adhesive sticky card...
May 31, 2016: Journal of Medical Entomology
Andrea Troupin, Berlin Londono-Renteria, Michael J Conway, Erin Cloherty, Samuel Jameson, Stephen Higgs, Dana L Vanlandingham, Erol Fikrig, Tonya M Colpitts
BACKGROUND: Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Aedes aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated...
September 2016: Biochimica et Biophysica Acta
Jesse Hwang, Kellie Ann Jurado, Erol Fikrig
Arboviruses have made unexpected reappearances in recent years. Unlike viruses that undergo direct transmission, arboviruses utilize an arthropod vector (e.g., mosquitos, sandflies, and ticks) to spread throughout human populations. Here, we provide a snapshot of mosquito susceptibility to viral infection using flaviviruses, alphaviruses, and bunyaviruses as examples of emerging pathogens of global health relevance.
May 11, 2016: Cell Host & Microbe
Alex Wagemakers, Joris Koetsveld, Sukanya Narasimhan, Melvin Wickel, Kathleen Deponte, Boris Bleijlevens, Seta Jahfari, Hein Sprong, Lyudmila S Karan, Denis S Sarksyan, Tom van der Poll, Linda K Bockenstedt, Adriaan D Bins, Alexander E Platonov, Erol Fikrig, Joppe W Hovius
Borrelia miyamotoi is a relapsing fever spirochete in Ixodes ticks that has been recently identified as a human pathogen causing hard tick-borne relapsing fever (HTBRF) across the Northern Hemisphere. No validated serologic test exists, and current serologic assays have low sensitivity in early HTBRF. To examine the humoral immune response against B. miyamotoi, we infected C3H/HeN mice with B. miyamotoi strain LB-2001 expressing variable small protein 1 (Vsp1) and demonstrated that spirochetemia was cleared after 3 d, coinciding with anti-Vsp1 IgM production...
May 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jeroen Coumou, Sukanya Narasimhan, Jos J Trentelman, Alex Wagemakers, Joris Koetsveld, Jasmin I Ersoz, Anneke Oei, Erol Fikrig, Joppe W Hovius
The causative agent of Lyme borreliosis, Borrelia burgdorferi, is transmitted by Ixodes ticks. During tick feeding, B. burgdorferi migrates from the tick gut to the salivary glands from where transmission to the host occurs. B. burgdorferi-interacting tick proteins might serve as vaccine targets to thwart B. burgdorferi transmission. A previous screening for B. burgdorferi-interacting Ixodes scapularis gut proteins identified an I. scapularis putative dystroglycan protein (ISCW015049). Here, we describe the ISCW015049's protein structure and its cellular location in the tick gut in relation to B...
March 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Penghua Wang, Shu Zhu, Long Yang, Shuang Cui, Wen Pan, Ruaidhri Jackson, Yunjiang Zheng, Anthony Rongvaux, Qiangming Sun, Guang Yang, Shandian Gao, Rongtuan Lin, Fuping You, Richard Flavell, Erol Fikrig
The nucleotide-binding oligomerization domain-like receptor (Nlrp) 6 maintains gut microbiota homeostasis and regulates antibacterial immunity. We now report a role for Nlrp6 in the control of enteric virus infection. Nlrp6(-/-) and control mice systemically challenged with encephalomyocarditis virus had similar mortality; however, the gastrointestinal tract of Nlrp6(-/-) mice exhibited increased viral loads. Nlrp6(-/-) mice orally infected with encephalomyocarditis virus had increased mortality and viremia compared with controls...
November 13, 2015: Science
Berlin Londono-Renteria, Andrea Troupin, Michael J Conway, Diana Vesely, Michael Ledizet, Christopher M Roundy, Erin Cloherty, Samuel Jameson, Dana Vanlandingham, Stephen Higgs, Erol Fikrig, Tonya M Colpitts
Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious human disease and mortality worldwide. There is no specific antiviral therapy or vaccine for DENV infection. Alterations in gene expression during DENV infection of the mosquito and the impact of these changes on virus infection are important events to investigate in hopes of creating new treatments and vaccines. We previously identified 203 genes that were ≥5-fold differentially upregulated during flavivirus infection of the mosquito...
October 2015: PLoS Pathogens
Sukanya Narasimhan, Erol Fikrig
Ticks are obligate blood-feeders and serve as vectors of human and livestock pathogens worldwide. Defining the tick microbiome and deciphering the interactions between the tick and its symbiotic bacteria in the context of tick development and pathogen transmission will likely reveal new insights and spawn new paradigms to control tick-borne diseases. Descriptive observations on the tick microbiome that began almost a century ago serve as forerunners to the gathering momentum to define the tick microbiome in greater detail...
July 2015: Trends in Parasitology
Wendy E Walker, Sebastian Kurscheid, Samit Joshi, Charlie A Lopez, Gerald Goh, Murim Choi, Lydia Barakat, John Francis, Ann Fisher, Michael Kozal, Heidi Zapata, Albert Shaw, Richard Lifton, Richard E Sutton, Erol Fikrig
UNLABELLED: Elite controllers (ECs) are a rare group of HIV seropositive individuals who are able to control viral replication without antiretroviral therapy. The mechanisms responsible for this phenotype, however, have not been fully elucidated. In this study, we examined CD4(+) T cell resistance to HIV in a cohort of elite controllers and explored transcriptional signatures associated with cellular resistance. We demonstrate that a subgroup of elite controllers possess CD4(+) T cells that are specifically resistant to R5-tropic HIV while remaining fully susceptible to X4-tropic and vesicular stomatitis virus G (VSV-G)-pseudotyped viruses...
May 2015: Journal of Virology
Martin Heisig, Sarah Mattessich, Alison Rembisz, Ali Acar, Martin Shapiro, Carmen J Booth, Girish Neelakanta, Erol Fikrig
Ectotherms in northern latitudes are seasonally exposed to cold temperatures. To improve survival under cold stress, they use diverse mechanisms to increase temperature resistance and prevent tissue damage. The accumulation of anti-freeze proteins that improve cold hardiness occurs in diverse species including plants, arthropods, fish, and amphibians. We previously identified an Ixodes scapularis anti-freeze glycoprotein, named IAFGP, and demonstrated its cold protective function in the natural tick host and in a transgenic Drosophila model...
2015: PloS One
Erol Fikrig, Audrey Turchick, Jen Czochor
No abstract text is available yet for this article.
December 2014: Yale Journal of Biology and Medicine
Martin Heisig, Nabil M Abraham, Lei Liu, Girish Neelakanta, Sarah Mattessich, Hameeda Sultana, Zhengling Shang, Juliana M Ansari, Charlotte Killiam, Wendy Walker, Lynn Cooley, Richard A Flavell, Herve Agaisse, Erol Fikrig
As microbial drug-resistance increases, there is a critical need for new classes of compounds to combat infectious diseases. The Ixodes scapularis tick antifreeze glycoprotein, IAFGP, functions as an antivirulence agent against diverse bacteria, including methicillin-resistant Staphylococcus aureus. Recombinant IAFGP and a peptide, P1, derived from this protein bind to microbes and alter biofilm formation. Transgenic iafgp-expressing flies and mice challenged with bacteria, as well as wild-type animals administered P1, were resistant to infection, septic shock, or biofilm development on implanted catheter tubing...
October 23, 2014: Cell Reports
Feng Qian, Gautam Goel, Hailong Meng, Xiaomei Wang, Fuping You, Lesley Devine, Khadir Raddassi, Melissa N Garcia, Kristy O Murray, Christopher R Bolen, Renaud Gaujoux, Shai S Shen-Orr, David Hafler, Erol Fikrig, Ramnik Xavier, Steven H Kleinstein, Ruth R Montgomery
West Nile virus (WNV) infection is usually asymptomatic but can cause severe neurological disease and death, particularly in older patients, and how individual variations in immunity contribute to disease severity is not yet defined. Animal studies identified a role for several immunity-related genes that determine the severity of infection. We have integrated systems-level transcriptional and functional data sets from stratified cohorts of subjects with a history of WNV infection to define whether these markers can distinguish susceptibility in a human population...
January 2015: Clinical and Vaccine Immunology: CVI
Alex Wagemakers, Anneke Oei, Michelle M Fikrig, Willem R Miellet, Joppe W Hovius
BACKGROUND: Borrelia miyamotoi is a relapsing fever spirochete found in Ixodes ticks in North America, Europe, and Asia, and has recently been found to be invasive in humans. Cultivation of this spirochete has not yet been described, but is important for patient diagnostics and scientific purposes. Host specificity of Borrelia species is dependent on resistance to host complement (serum resistance), and since B. miyamotoi has been identified as a human pathogen we were interested whether B...
2014: Parasites & Vectors
Sukanya Narasimhan, Jeroen Coumou, Tim J Schuijt, Eric Boder, Joppe W Hovius, Erol Fikrig
Borrelia burgdorferi transmission to the vertebrate host commences with growth of the spirochete in the tick gut and migration from the gut to the salivary glands. This complex process, involving intimate interactions of the spirochete with the gut epithelium, is pivotal to transmission. We utilized a yeast surface display library of tick gut proteins to perform a global screen for tick gut proteins that might interact with Borrelia membrane proteins. A putative fibronectin type III domain-containing tick gut protein (Ixofin3D) was most frequently identified from this screen and prioritized for further analysis...
August 2014: PLoS Pathogens
Michelle W M Li, Jiuling Wang, Yang O Zhao, Erol Fikrig
The Toll and IMD pathways are known to be induced upon Plasmodium berghei and Plasmodium falciparum infection, respectively. It is unclear how Plasmodium or other pathogens in the blood meal and their invasion of the midgut epithelium would trigger the innate immune responses in immune cells, in particular hemocytes. Gap junctions, which can mediate both cell-to-cell and cell-to-extracellular communication, may participate in this signal transduction. This study examined whether innexins, gap junction proteins in insects, are involved in anti-Plasmodium responses in Anopheles gambiae...
September 5, 2014: Journal of Biological Chemistry
Peter J Krause, Sukanya Narasimhan, Gary P Wormser, Alan G Barbour, Alexander E Platonov, Janna Brancato, Timothy Lepore, Kenneth Dardick, Mark Mamula, Lindsay Rollend, Tanner K Steeves, Maria Diuk-Wasser, Sahar Usmani-Brown, Phillip Williamson, Denis S Sarksyan, Erol Fikrig, Durland Fish
Borrelia miyamotoi sensu lato, a relapsing fever Borrelia sp., is transmitted by the same ticks that transmit B. burgdorferi (the Lyme disease pathogen) and occurs in all Lyme disease-endemic areas of the United States. To determine the seroprevalence of IgG against B. miyamotoi sensu lato in the northeastern United States and assess whether serum from B. miyamotoi sensu lato-infected persons is reactive to B. burgdorferi antigens, we tested archived serum samples from area residents during 1991-2012. Of 639 samples from healthy persons, 25 were positive for B...
July 2014: Emerging Infectious Diseases
David Seidman, Nore Ojogun, Naomi J Walker, Juliana Mastronunzio, Amandeep Kahlon, Kathryn S Hebert, Sophia Karandashova, Daniel P Miller, Brittney K Tegels, Richard T Marconi, Erol Fikrig, Dori L Borjesson, Jason A Carlyon
Anaplasma phagocytophilum, which causes granulocytic anaplasmosis in humans and animals, is a tick-transmitted obligate intracellular bacterium that mediates its own uptake into neutrophils and non-phagocytic cells. Invasins of obligate intracellular pathogens are attractive targets for protecting against or curing infection because blocking the internalization step prevents survival of these organisms. The complement of A. phagocytophilum invasins is incompletely defined. Here, we report the significance of a novel A...
August 2014: Cellular Microbiology
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