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https://www.readbyqxmd.com/read/29032540/artificial-infection-of-ticks-with-borrelia-burgdorferi-using-a-microinjection-method-and-their-detection-in-vivo-using-quantitative-pcr-targeting-flab-rna
#1
Alexis A Smith, Xiuli Yang, Erol Fikrig, Utpal Pal
Borrelia burgdorferi is maintained in nature by a tick-rodent infection cycle where it traverses and colonizes a variety of host and vector tissues. A tick-borne murine model has been developed to study Lyme disease in the laboratory, which has a substantial impact in advancing our knowledge of spirochete infectivity and pathogenesis. Here, we detail a microinjection-based method for rapid and efficient infection of ticks with B. burgdorferi. While laboratory generation of B. burgdorferi-infected nymphs via natural larval engorgement on infected hosts and subsequent molting could take several weeks to months, the microinjection-based infection procedure requires only a few hours to generate infected ticks and allows introduction of defined quantities of spirochetes, including mutant isolates that are attenuated for infection in mice and thus cannot be naturally acquired by ticks...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28775250/modulation-of-the-tick-gut-milieu-by-a-secreted-tick-protein-favors-borrelia-burgdorferi-colonization
#2
Sukanya Narasimhan, Tim J Schuijt, Nabil M Abraham, Nallakkandi Rajeevan, Jeroen Coumou, Morven Graham, Andrew Robson, Ming-Jie Wu, Sirlei Daffre, Joppe W Hovius, Erol Fikrig
The Lyme disease agent, Borrelia burgdorferi, colonizes the gut of the tick Ixodes scapularis, which transmits the pathogen to vertebrate hosts including humans. Here we show that B. burgdorferi colonization increases the expression of several tick gut genes including pixr, encoding a secreted gut protein with a Reeler domain. RNA interference-mediated silencing of pixr, or immunity against PIXR in mice, impairs the ability of B. burgdorferi to colonize the tick gut. PIXR inhibits bacterial biofilm formation in vitro and in vivo...
August 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28656018/zika-virus-and-sexual-transmission-a-new-route-of-transmission-for-mosquito-borne-flaviviruses%C3%A2
#3
REVIEW
Andrew K Hastings, Erol Fikrig
Beginning in 2015, concern over a new global epidemic has spread in the media, governmental agencies, legislative bodies and the public at large. This newly emerging threat has been reported to cause symptoms ranging from mild fever, rash, and body aches, to severe birth defects and acute onset paralysis. The causative agent of this disease, Zika virus, is closely related to two other important human pathogens, dengue and West Nile Virus (WNV), but has some distinguishing features that has raised alarms from the scientific community...
June 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28636595/nlrp9b-inflammasome-restricts-rotavirus-infection-in-intestinal-epithelial-cells
#4
Shu Zhu, Siyuan Ding, Penghua Wang, Zheng Wei, Wen Pan, Noah W Palm, Yi Yang, Hua Yu, Hua-Bing Li, Geng Wang, Xuqiu Lei, Marcel R de Zoete, Jun Zhao, Yunjiang Zheng, Haiwei Chen, Yujiao Zhao, Kellie A Jurado, Ningguo Feng, Liang Shan, Yuval Kluger, Jun Lu, Clara Abraham, Erol Fikrig, Harry B Greenberg, Richard A Flavell
Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown...
June 29, 2017: Nature
https://www.readbyqxmd.com/read/28634573/tick-bioactive-molecules-as-novel-therapeutics-beyond-vaccine-targets
#5
Kristen E Murfin, Erol Fikrig
No abstract text is available yet for this article.
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28623344/an-essential-role-of-pi3k-in-the-control-of-west-nile-virus-infection
#6
Leilei Wang, Long Yang, Erol Fikrig, Penghua Wang
The phosphatidyl-inositol-3 kinases (PI3K) pathway regulates a variety of cellular processes, including cell proliferation, RNA processing, protein translation, autophagy, apoptosis and antiviral immunity. Many viruses depend on PI3K signaling for replication. However, its role in flaviviral infection has not been clearly defined. Here we report that PI3K signaling is critical for the control of West Nile virus (WNV) infection by regulating type I IFN (IFN-I) response. Inhibition of PI3K activity by 3-methyl adenine (3-MA), Wortmannin (WM) and LY294002 (LY) increased viral titers by 3-16 folds in primary mouse macrophages, embryonic fibroblasts and human cell lines...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28472297/fetal-growth-restriction-caused-by-sexual-transmission-of-zika-virus-in-mice
#7
Ryuta Uraki, Kellie Ann Jurado, Jesse Hwang, Klara Szigeti-Buck, Tamas L Horvath, Akiko Iwasaki, Erol Fikrig
Zika virus (ZIKV) can be transmitted by mosquito bite or sexual contact. Using mice that lack the type I interferon receptor, we examined sexual transmission of ZIKV. Electron microscopy analyses showed association of virions with developing sperm within testes as well as with mature sperm within epididymis. When ZIKV-infected male mice were mated with naive female mice, the weight of fetuses at embryonic day 18.5 was significantly reduced compared with the control group. Additionally, we found ocular deformities in a minority of the fetuses...
June 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28438938/a-tick-antivirulence-protein-potentiates-antibiotics-against-staphylococcus-aureus
#8
Nabil M Abraham, Lei Liu, Brandon L Jutras, Kristen Murfin, Ali Acar, Timur O Yarovinsky, Erica Sutton, Martin Heisig, Christine Jacobs-Wagner, Erol Fikrig
New strategies are needed to combat antibiotic resistance, especially against pathogens such as methicillin-resistant Staphylococcus aureus A tick antifreeze glycoprotein, IAFGP, possesses potent antibiofilm properties against a variety of clinical pathogens, including S. aureus Synergy between IAFGP, or a peptide (P1) representative of a repeat region of the protein, with different antibiotics was assessed in vitro Antibiotics that synergized with either IAFPG or P1 were further evaluated in vivo using vertebrate and invertebrate infection models...
July 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28423319/tam-receptors-are-not-required-for-zika-virus-infection-in-mice
#9
Andrew K Hastings, Laura J Yockey, Brett W Jagger, Jesse Hwang, Ryuta Uraki, Hallie F Gaitsch, Lindsay A Parnell, Bin Cao, Indira U Mysorekar, Carla V Rothlin, Erol Fikrig, Michael S Diamond, Akiko Iwasaki
Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl(-/-), Mertk(-/-), Axl(-/-)Mertk(-/-), and Axl(-/-)Tyro3(-/-) mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28392782/anti-biofilm-activity-of-a-self-aggregating-peptide-against-streptococcus-mutans
#10
Juliana M Ansari, Nabil M Abraham, Jenna Massaro, Kelsey Murphy, Jillian Smith-Carpenter, Erol Fikrig
Streptococcus mutans is the primary agent of dental cavities, in large part due to its ability to adhere to teeth and create a molecular scaffold of glucan polysaccharides on the tooth surface. Disrupting the architecture of S. mutans biofilms could help undermine the establishment of biofilm communities that cause cavities and tooth decay. Here we present a synthetic peptide P1, derived from a tick antifreeze protein, which significantly reduces S. mutans biofilm formation. Incubating cells with this peptide decreased biofilm biomass by approximately 75% in both a crystal violet microplate assay and an in vitro tooth model using saliva-coated hydroxyapatite discs...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28261663/zika-virus-causes-testicular-atrophy
#11
Ryuta Uraki, Jesse Hwang, Kellie Ann Jurado, Sarah Householder, Laura J Yockey, Andrew K Hastings, Robert J Homer, Akiko Iwasaki, Erol Fikrig
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has recently been found to cause fetal infection and neonatal abnormalities, including microcephaly and neurological dysfunction. ZIKV persists in the semen months after the acute viremic phase in humans. To further understand the consequences of ZIKV persistence in males, we infected Ifnar1(-/-) mice via subcutaneous injection of a pathogenic but nonlethal ZIKV strain. ZIKV replication persists within the testes even after clearance from the blood, with interstitial, testosterone-producing Leydig cells supporting virus replication...
February 2017: Science Advances
https://www.readbyqxmd.com/read/28195158/infection-derived-lipids-elicit-an-immune-deficiency-circuit-in-arthropods
#12
Dana K Shaw, Xiaowei Wang, Lindsey J Brown, Adela S Oliva Chávez, Kathryn E Reif, Alexis A Smith, Alison J Scott, Erin E McClure, Vishant M Boradia, Holly L Hammond, Eric J Sundberg, Greg A Snyder, Lei Liu, Kathleen DePonte, Margarita Villar, Massaro W Ueti, José de la Fuente, Robert K Ernst, Utpal Pal, Erol Fikrig, Joao H F Pedra
The insect immune deficiency (IMD) pathway resembles the tumour necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties activate the IMD signalling cascade remains unknown. Here, we show that infection-derived lipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 1-palmitoyl-2-oleoyl diacylglycerol (PODAG) stimulate the IMD pathway of ticks. The tick IMD network protects against colonization by three distinct bacteria, that is the Lyme disease spirochete Borrelia burgdorferi and the rickettsial agents Anaplasma phagocytophilum and A...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28152074/multiple-ubxn-family-members-inhibit-retrovirus-and-lentivirus-production-and-canonical-nf%C3%AE%C2%BA%C3%AE-signaling-by-stabilizing-i%C3%AE%C2%BAb%C3%AE
#13
Yani Hu, Kaitlin O'Boyle, Jim Auer, Sagar Raju, Fuping You, Penghua Wang, Erol Fikrig, Richard E Sutton
UBXN proteins likely participate in the global regulation of protein turnover, and we have shown that UBXN1 interferes with RIG-I-like receptor (RLR) signaling by interacting with MAVS and impeding its downstream effector functions. Here we demonstrate that over-expression of multiple UBXN family members decreased lentivirus and retrovirus production by several orders-of-magnitude in single cycle assays, at the level of long terminal repeat-driven transcription, and three family members, UBXN1, N9, and N11 blocked the canonical NFκB pathway by binding to Cullin1 (Cul1), inhibiting IκBα degradation...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28096373/pathogen-mediated-manipulation-of-arthropod-microbiota-to-promote-infection
#14
Nabil M Abraham, Lei Liu, Brandon Lyon Jutras, Akhilesh K Yadav, Sukanya Narasimhan, Vissagan Gopalakrishnan, Juliana M Ansari, Kimberly K Jefferson, Felipe Cava, Christine Jacobs-Wagner, Erol Fikrig
Arthropods transmit diverse infectious agents; however, the ways microbes influence their vector to enhance colonization are poorly understood. Ixodes scapularis ticks harbor numerous human pathogens, including Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis. We now demonstrate that A. phagocytophilum modifies the I. scapularis microbiota to more efficiently infect the tick. A. phagocytophilum induces ticks to express Ixodes scapularis antifreeze glycoprotein (iafgp), which encodes a protein with several properties, including the ability to alter bacterial biofilm formation...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095875/assessment-of-synthetic-floral-based-attractants-and-sugar-baits-to-capture-male-and-female-aedes-aegypti-diptera-culicidae
#15
Kara Fikrig, Brian J Johnson, Durland Fish, Scott A Ritchie
BACKGROUND: The viruses transmitted by Aedes aegypti, including dengue and Zika viruses, are rapidly expanding in geographic range and as a threat to public health. In response, control programs are increasingly turning to the use of sterile insect techniques resulting in a need to trap male Ae. aegypti to monitor the efficacy of the intervention. However, there is a lack of effective and cheap methods for trapping males. Thus, we attempted to exploit the physiological need to obtain energy from sugar feeding in order to passively capture male and female Ae...
January 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/27966815/zika-virus-infection-of-hofbauer-cells
#16
Michael K Simoni, Kellie Ann Jurado, Vikki M Abrahams, Erol Fikrig, Seth Guller
Recent studies have linked antenatal infection with Zika virus (ZIKV) with major adverse fetal and neonatal outcomes, including microcephaly. There is a growing consensus for the existence of a congenital Zika syndrome (CZS). Previous studies have indicated that non-placental macrophages play a key role in the replication of dengue virus (DENV), a closely related flavivirus. As the placenta provides the conduit for vertical transmission of certain viruses, and placental Hofbauer cells (HBCs) are fetal-placental macrophages located adjacent to fetal capillaries, it is not surprising that several recent studies have examined infection of HBCs by ZIKV...
February 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/27798161/tlr8-couples-socs-1-and-restrains-tlr7-mediated-antiviral-immunity-exacerbating-west-nile-virus-infection-in-mice
#17
Amber M Paul, Dhiraj Acharya, Linda Le, Penghua Wang, Dobrivoje S Stokic, A Arturo Leis, Lena Alexopoulou, Terrence Town, Richard A Flavell, Erol Fikrig, Fengwei Bai
West Nile virus (WNV) is a neurotropic ssRNA flavivirus that can cause encephalitis, meningitis, and death in humans and mice. Human TLR7 and TLR8 and mouse TLR7 recognize viral ssRNA motifs and induce antiviral immunity. However, the role of mouse TLR8 in antiviral immunity is poorly understood. In this article, we report that TLR8-deficient (Tlr8(-/-)) mice were resistant to WNV infection compared with wild-type controls. Efficient WNV clearance and moderate susceptibility to WNV-mediated neuronal death in Tlr8(-/-) mice were attributed to overexpression of Tlr7 and IFN-stimulated gene-56 expression, whereas reduced expression of the proapoptotic gene coding Bcl2-associated X protein was observed...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27795421/interleukin-17a-promotes-cd8-t-cell-cytotoxicity-to-facilitate-west-nile-virus-clearance
#18
Dhiraj Acharya, Penghua Wang, Amber M Paul, Jianfeng Dai, David Gate, Jordan E Lowery, Dobrivoje S Stokic, A Arturo Leis, Richard A Flavell, Terrence Town, Erol Fikrig, Fengwei Bai
CD8(+) T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8(+) T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a(-/-)) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8(+) T cells isolated from Il17a(-/-) mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in vivo Importantly, treatment of WNV-infected mice with recombinant IL-17A, as late as day 6 postinfection, significantly reduces the viral burden and increases survival, suggesting a therapeutic potential for IL-17A...
January 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27632170/aedes-aegypti-d7-saliva-protein-inhibits-dengue-virus-infection
#19
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
https://www.readbyqxmd.com/read/27595140/zika-virus-productively-infects-primary-human-placenta-specific-macrophages
#20
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
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