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https://www.readbyqxmd.com/read/29760192/circadian-rhythms-influence-the-severity-of-sepsis-in-mice-via-a-tlr2-dependent-leukocyte-intrinsic-mechanism
#1
Erica L Heipertz, Jourdan Harper, Charlie A Lopez, Erol Fikrig, Michael E Hughes, Wendy E Walker
Circadian rhythms coordinate an organism's activities and biological processes to the optimal time in the 24-h daylight cycle. We previously demonstrated that male C57BL/6 mice develop sepsis more rapidly when the disease is induced in the nighttime versus the daytime. In this report, we elucidate the mechanism of this diurnal difference. Sepsis was induced via cecal ligation and puncture (CLP) at zeitgeber time (ZT)-19 (2 am) or ZT-7 (2 pm). Like the males used in our prior study, female C57BL/6 mice had a worse outcome when CLP was induced at ZT-19 versus ZT-7, and these effects persisted when we pooled the data from both sexes...
May 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29649443/immunization-with-agtrio-a-protein-in-anopheles-saliva-contributes-to-protection-against-plasmodium-infection-in-mice
#2
Srdjan M Dragovic, Tolulope A Agunbiade, Marianna Freudzon, Jing Yang, Andrew K Hastings, Tyler R Schleicher, Xia Zhou, Sam Craft, Yu-Min Chuang, Floricel Gonzalez, Youquan Li, Gabriela Hrebikova, Abhai Tripathi, Godfree Mlambo, Lionel Almeras, Alexander Ploss, George Dimopoulos, Erol Fikrig
Plasmodium infection begins with the bite of an anopheline mosquito, when sporozoites along with saliva are injected into a vertebrate host. The role of the host responses to mosquito saliva components in malaria remains unclear. We observed that antisera against Anopheles gambiae salivary glands partially protected mice from mosquito-borne Plasmodium infection. Specifically, antibodies to A. gambiae TRIO (AgTRIO), a mosquito salivary gland antigen, contributed to the protection. Mice administered AgTRIO antiserum showed lower Plasmodium liver burden and decreased parasitemia when exposed to infected mosquitoes...
April 11, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29606496/small-interfering-rna-mediated-control-of-virus-replication-in-the-cns-is-therapeutic-and-enables-natural-immunity-to-west-nile-virus
#3
Jagadish Beloor, Nyree Maes, Irfan Ullah, Pradeep Uchil, Andrew Jackson, Erol Fikrig, Sang Kyung Lee, Priti Kumar
No vaccines or therapeutics are licensed for West Nile virus (WNV), a mosquito-transmitted neuroencephalitic flavivirus. The small interfering RNA siFvEJW targets a conserved sequence within the WNV E protein and limits virus infection. Using a rabies virus-derived neuron-targeting peptide (RVG9R) and an intranasal route for delivering siFvEJW to the CNS, we demonstrate that treatment of WNV-infected mice at late stages of neuroinvasive disease results in recovery. Selectively targeting virus in the CNS lowers viral burdens in the brain, reduces neuropathology, and results in a 90% survival rate at 5-6 days post-infection (when viral titers peak in the CNS), while placebo-treated mice succumb by days 9-10...
March 21, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29505571/altered-vector-competence-in-an-experimental-mosquito-mouse-transmission-model-of-zika-infection
#4
Ryuta Uraki, Andrew K Hastings, Andrea Gloria-Soria, Jeffrey R Powell, Erol Fikrig
Few animal models of Zika virus (ZIKV) infection have incorporated arthropod-borne transmission. Here, we establish an Aedes aegypti mosquito model of ZIKV infection of mice, and demonstrate altered vector competency among three strains, (Orlando, ORL, Ho Chi Minh, HCM, and Patilas, PAT). All strains acquired ZIKV in their midguts after a blood meal from infected mice, but ZIKV transmission only occurred in mice fed upon by HCM, and to a lesser extent PAT, but not ORL, mosquitoes. This defect in transmission from ORL or PAT mosquitoes was overcome by intrathoracic injection of ZIKV into mosquito...
March 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29420552/human-borrelia-miyamotoi-infection-in-california-serodiagnosis-is-complicated-by-multiple-endemic-borrelia-species
#5
Peter J Krause, Madeleine Carroll, Natalia Fedorova, Janna Brancato, Cecilia Dumouchel, Fredua Akosa, Sukanya Narasimhan, Erol Fikrig, Robert S Lane
To determine whether human Borrelia miyamotoi infection occurs in the far-western United States, we tested archived sera from northwestern California residents for antibodies to this emerging relapsing fever spirochete. These residents frequently were exposed to I. pacificus ticks in a region where B. miyamotoi tick infection has been reported. We used a two-step B. miyamotoi rGlpQ assay and a B. miyamotoi whole-cell lysate (WCL) assay to detect B. miyamotoi antibody. We also employed Borrelia hermsii and Borrelia burgdorferi WCL assays to examine if these Borrelia induce cross reacting antibody to B...
2018: PloS One
https://www.readbyqxmd.com/read/29305462/type-i-interferons-instigate-fetal-demise-after-zika-virus-infection
#6
Laura J Yockey, Kellie A Jurado, Nitin Arora, Alon Millet, Tasfia Rakib, Kristin M Milano, Andrew K Hastings, Erol Fikrig, Yong Kong, Tamas L Horvath, Scott Weatherbee, Harvey J Kliman, Carolyn B Coyne, Akiko Iwasaki
Zika virus (ZIKV) infection during pregnancy is associated with adverse fetal outcomes, including microcephaly, growth restriction, and fetal demise. Type I interferons (IFNs) are essential for host resistance against ZIKV, and IFN-α/β receptor (IFNAR)-deficient mice are highly susceptible to ZIKV infection. Severe fetal growth restriction with placental damage and fetal resorption is observed after ZIKV infection of type I IFN receptor knockout ( Ifnar1 -/- ) dams mated with wild-type sires, resulting in fetuses with functional type I IFN signaling...
January 5, 2018: Science Immunology
https://www.readbyqxmd.com/read/29228208/advances-in-serodiagnostic-testing-for-lyme-disease-are-at-hand
#7
John A Branda, Barbara A Body, Jeff Boyle, Bernard M Branson, Raymond J Dattwyler, Erol Fikrig, Noel J Gerald, Maria Gomes-Solecki, Martin Kintrup, Michel Ledizet, Andrew E Levin, Michael Lewinski, Lance A Liotta, Adriana Marques, Paul S Mead, Emmanuel F Mongodin, Segaran Pillai, Prasad Rao, William H Robinson, Kristian M Roth, Martin E Schriefer, Thomas Slezak, Jessica Snyder, Allen C Steere, Jan Witkowski, Susan J Wong, Steven E Schutzer
The cause of Lyme disease, Borrelia burgdorferi, was discovered in 1983. A 2-tiered testing protocol was established for serodiagnosis in 1994, involving an enzyme immunoassay (EIA) or indirect fluorescence antibody, followed (if reactive) by immunoglobulin M and immunoglobulin G Western immunoblots. These assays were prepared from whole-cell cultured B. burgdorferi, lacking key in vivo expressed antigens and expressing antigens that can bind non-Borrelia antibodies. Additional drawbacks, particular to the Western immunoblot component, include low sensitivity in early infection, technical complexity, and subjective interpretation when scored by visual examination...
March 19, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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