Research Topics
Genomes and Genes
| Erol FikrigSummaryAffiliation: Yale University Country: USA Publications
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Publications
Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferiZhiming Ouyang
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
BMC Microbiol 12:44. 2012..burgdorferi, has been lacking...
Borrelia burgdorferi--traveling incognito?Erol Fikrig
Section of Rheumatology, Department of Medicine, Yale University School of Medicine, Room 525A, 300 Cedar Street, New Haven, CT 06520 8031, USA
Microbes Infect 8:1390-9. 2006..The survival strategies utilized by the spirochete during transmission and the initial stages of infection are discussed...
Preferential presence of decorin-binding protein B (BBA25) and BBA50 antibodies in cerebrospinal fluid of patients with neurologic Lyme diseaseErol Fikrig
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
J Clin Microbiol 42:1243-6. 2004..Decorin-binding protein B (BBA25) and BBA50 (hypothetical protein) elicited immunoglobulin G (IgG) or IgM detectable in CSF-but not sera-of patients, demonstrating preferential antibody production during neuroborreliosis...
Outer surface protein B is critical for Borrelia burgdorferi adherence and survival within Ixodes ticksGirish Neelakanta
Section of Rheumatology, Yale University School of Medicine, New Haven, Connecticut, United States of America
PLoS Pathog 3:e33. 2007..Taken together, these data suggest that OspB has an important role within Ixodes scapularis and that B. burgdorferi relies upon multiple genes to efficiently persist in ticks...
Antibodies against a tick protein, Salp15, protect mice from the Lyme disease agentJianfeng Dai
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Cell Host Microbe 6:482-92. 2009....
Fusion loop peptide of the West Nile virus envelope protein is essential for pathogenesis and is recognized by a therapeutic cross-reactive human monoclonal antibodyHameeda Sultana
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
J Immunol 183:650-60. 2009..These experiments define the molecular determinant on the envelope protein recognized by mAb11 and demonstrate the importance of this region in causing West Nile encephalitis...
Antibodies targeting linear determinants of the envelope protein protect mice against West Nile virusMichel Ledizet
L2 Diagnostics, Department of Internal Medicine, Yale School of Medicine, 300 George Street, New Haven, CT 06525, USA
J Infect Dis 196:1741-8. 2007..These immunoglobulins recognized the E proteins of related flaviviruses, demonstrating that antibodies targeting specific E protein epitopes could be developed for prevention and treatment of multiple flavivirus infections...
The Lyme disease agent exploits a tick protein to infect the mammalian hostNandhini Ramamoorthi
Sections of Rheumatology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Nature 436:573-7. 2005..scapularis drastically reduced the capacity of tick-borne spirochaetes to infect mice. These results show the capacity of a pathogen to use a secreted arthropod protein to help it colonize the mammalian host...
Borrelia burgdorferi outer surface protein (osp) B expression independent of ospAFang Ting Liang
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8031, USA
Microb Pathog 37:35-40. 2004..This was consistent with the analysis of antibody responses to the two lipoproteins, which showed a more frequent OspB response than OspA during chronic murine infection...
Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glandsLei Liu
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, PO Box 208022, New Haven, Connecticut 06520 8022, USA
EMBO Rep 12:1196-203. 2011..This report provides new insights into A. phagocytophilum infection of ticks and reveals new avenues to interrupt the life cycle of Anaplasma and related Rickettsial pathogens...
Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticksHameeda Sultana
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
J Exp Med 207:1727-43. 2010....
TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferiUtpal Pal
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Cell 119:457-68. 2004..Identification of an I. scapularis receptor for B. burgdorferi is the first step toward elucidating arthropod ligands that are required for survival of spirochetes in nature...
A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agentTim J Schuijt
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06420, USA
Cell Host Microbe 10:136-46. 2011....
Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritisUtpal Pal
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
J Exp Med 205:133-41. 2008..These data delineate a role for differentially produced B. burgdorferi antigens in spirochete colonization of mouse joints, and suggest new strategies for the treatment of Lyme arthritis...
Toll-like receptor 7 mitigates lethal West Nile encephalitis via interleukin 23-dependent immune cell infiltration and homingTerrence Town
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
Immunity 30:242-53. 2009..Collectively, these results demonstrate that TLR7 and IL-23-dependent WNV responses represent a vital host defense mechanism that operates by affecting immune cell homing to infected target cells...
Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine responseAlexander Panda
Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA
J Immunol 184:2518-27. 2010....
A tick antioxidant facilitates the Lyme disease agent's successful migration from the mammalian host to the arthropod vectorSukanya Narasimhan
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Cell Host Microbe 2:7-18. 2007..burgdorferi at the tick feeding site in mice. These data demonstrate that pathogens can exploit arthropod molecules to defuse mammalian responses in order to successfully enter the vector...
OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glandsUtpal Pal
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
J Clin Invest 113:220-30. 2004..These studies conclusively demonstrate the importance of OspC in the invasion of tick salivary glands by B. burgdorferi, a critical step in the transmission of spirochetes from the arthropod vector to the mammalian host...
IL-22 signaling contributes to West Nile encephalitis pathogenesisPenghua Wang
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
PLoS ONE 7:e44153. 2012..Our results suggest that IL-22 signaling exacerbates lethal WNV encephalitis likely by promoting WNV neuroinvasion...
An in vivo transfection approach elucidates a role for Aedes aegypti thioester-containing proteins in flaviviral infectionGong Cheng
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America
PLoS ONE 6:e22786. 2011..In vivo transfection of AeTEP-1 into Ae. aegypti significantly reduced dengue virus infection, suggesting that the approach can further our understanding of pathogen-mosquito interactions...
Toll-like receptors 1 and 2 heterodimers alter Borrelia burgdorferi gene expression in mice and ticksErol Fikrig
Section of Infectious Diseases, Department of Internal Medicine, 2Howard Hughes Medical Institute, and 3Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut
J Infect Dis 200:1331-40. 2009....
Antiviral peptides targeting the west nile virus envelope proteinFengwei Bai
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
J Virol 81:2047-55. 2007..These short peptides serve as the basis for developing new therapeutics for West Nile encephalitis and, potentially, other flaviviruses...
The Lyme disease agent Borrelia burgdorferi requires BB0690, a Dps homologue, to persist within ticksXin Li
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8031, USA
Mol Microbiol 63:694-710. 2007..Dps is critical for spirochaete persistence within ticks, and strategies to interfere with Dps could potentially reduce Borrelia populations in nature and thereby influence the incidence of Lyme disease...
Role of outer surface protein D in the Borrelia burgdorferi life cycleXin Li
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520 8031, USA
Infect Immun 75:4237-44. 2007..These data suggest that B. burgdorferi can compensate for the lack of OspD in both ticks and mice and that OspD may have a nonessential, secondary, role in B. burgdorferi persistence within I. scapularis...
ASC/PYCARD and caspase-1 regulate the IL-18/IFN-gamma axis during Anaplasma phagocytophilum infectionJoao H F Pedra
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
J Immunol 179:4783-91. 2007..phagocytophilum. Taken together, our data demonstrate that ASC and caspase-1 are critical for IFN-gamma-mediated control of A. phagocytophilum infection...
c-Jun NH2-terminal kinase 2 inhibits gamma interferon production during Anaplasma phagocytophilum infectionJoao H F Pedra
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Infect Immun 76:308-16. 2008..Collectively, these findings provide strong evidence that JNK2 is an important regulatory protein for IFN-gamma secretion upon challenge with A. phagocytophilum...
Dysregulation of TLR3 impairs the innate immune response to West Nile virus in the elderlyKok Fai Kong
Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520 8031, USA
J Virol 82:7613-23. 2008..This alteration of the innate immune response with aging may contribute to the permeability of the blood-brain barrier and suggests a possible mechanism for the increased severity of WNV infection in older individuals...
Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-IPenghua Wang
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
Nat Immunol 11:912-9. 2010....
A recombinant envelope protein vaccine against West Nile virusMichel Ledizet
L2 Diagnostics, LLC, 300 George Street, New Haven, CT 06511, USA
Vaccine 23:3915-24. 2005..This recombinant form of E protein, combined with aluminum hydroxide, is a candidate vaccine that may protect humans and horses against WN virus infections...
A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF+ cellsNathalie Bonafe
L2 Diagnostics, LLC, 300 George Street, New Haven, CT 06511, USA
Vaccine 27:213-22. 2009..These observations demonstrate that baculovirus-produced rWNV-E can be formulated with aluminum hydroxide to produce a stable and safe vaccine which induces humoral immunity that can protect against WNV infection...
An Ixodes scapularis protein required for survival of Anaplasma phagocytophilum in tick salivary glandsBindu Sukumaran
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
J Exp Med 203:1507-17. 2006..These data demonstrate the specific requirement of a pathogen for a tick salivary protein to persist within the arthropod and provide a paradigm for understanding how Rickettsia-like pathogens are maintained within vectors...
Disruption of the salivary protein 14 in Ixodes scapularis nymphs and impact on pathogen acquisitionJoao H F Pedra
Section of Rheumatology and Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8031, USA
Am J Trop Med Hyg 75:677-82. 2006..B. burgdorferi and A. phagocytophilum acquisition was not affected 72 hours after feeding. Our results suggest that different mechanisms govern nymph and adult feeding in I. scapularis...
A paradoxical role for neutrophils in the pathogenesis of West Nile virusFengwei Bai
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8031, USA
J Infect Dis 202:1804-12. 2010..Collectively, these data suggest that PMNs have a biphasic response to WNV infection, serving as a reservoir for replication and dissemination in early infection and later contributing to viral clearance...
Antibodies to whole-cell or recombinant antigens of Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti in white-footed miceLouis A Magnarelli
Department of Entomology, The Connecticut Agricultural Experiment Station, PO Box 1106, New Haven, Connecticut 06504, USA
J Wildl Dis 42:732-8. 2006..leucopus, separate incorporation of these fusion proteins in an ELISA was very helpful in confirming past or current infections and in identifying specific foci for B. burgdorferi and A. phagocytophilum...
Molecular interactions that enable movement of the Lyme disease agent from the tick gut into the hemolymphLili Zhang
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America
PLoS Pathog 7:e1002079. 2011..burgdorferi burden in the tick hemolymph. Delineating the specific spirochete and arthropod ligands required for B. burgdorferi movement in the tick may lead to new strategies to interrupt the life cycle of the Lyme disease agent...
OspB antibody prevents Borrelia burgdorferi colonization of Ixodes scapularisErol Fikrig
Section of Rheumatology, Department of Internal Medicine. Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Infect Immun 72:1755-9. 2004..burgdorferi colonization of I. scapularis, highlighting a specific role for OspB in spirochete- arthropod interactions and suggesting new antibody-mediated strategies for interfering with B. burgdorferi transmission...
IL-10 signaling blockade controls murine West Nile virus infectionFengwei Bai
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America
PLoS Pathog 5:e1000610. 2009..In conclusion, IL-10 signaling plays a negative role in immunity against WNV infection, and blockade of IL-10 signaling by genetic or pharmacologic means helps to control viral infection, suggesting a novel anti-WNV therapeutic strategy...
Borrelia burgdorferi changes its surface antigenic expression in response to host immune responsesFang Ting Liang
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA
Infect Immun 72:5759-67. 2004..This change in antigenic expression could be induced by passively immunizing infected severe combined immunodeficiency mice with specific Borrelia antisera or OspC antibody and appears to allow B. burgdorferi to resist immune attack...
West Nile virus envelope protein inhibits dsRNA-induced innate immune responsesAlvaro Arjona
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
J Immunol 179:8403-9. 2007..In conclusion, these data show that the major structural protein of WNV impairs the innate immune response and suggest that WNV exploits differential vector/host E glycosylation profiles to evade antiviral mechanisms...
IL-12/23p40-dependent clearance of Anaplasma phagocytophilum in the murine model of human anaplasmosisJoao H F Pedra
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
FEMS Immunol Med Microbiol 50:401-10. 2007..The IL-12/23p40 subunit drives the CD4(+) Th1 immune response in the early phase of infection and IL-12/23p40-independent mechanisms ultimately contribute to pathogen elimination from the host...
Matrix metalloproteinase 9 facilitates West Nile virus entry into the brainPenghua Wang
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
J Virol 82:8978-85. 2008..These data suggest that MMP9 plays a role in mediating WNV entry into the central nervous system and that strategies to interrupt this process may influence the course of West Nile encephalitis...
Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacyStacey L Demento
Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA
Vaccine 27:3013-21. 2009..The design of such an antigen delivery mechanism with the ability to stimulate two potent innate immune pathways represents a potent new approach to simultaneous antigen and adjuvant delivery...
The Lyme disease vaccine takes its tollVenetta Thomas
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA
Vector Borne Zoonotic Dis 2:217-22. 2002..These data suggest that defects in the TLR1/2 signaling pathway are associated with an impaired ability to generate antibodies following immunization with OspA lipoprotein...
Ixodes scapularis JAK-STAT pathway regulates tick antimicrobial peptides, thereby controlling the agent of human granulocytic anaplasmosisLei Liu
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
J Infect Dis 206:1233-41. 2012..These data suggest that the JAK-STAT signaling pathway plays a key role in controlling A. phagocytophilum infection in ticks by regulating the expression of antimicrobial peptides...
Anaplasma phagocytophilum increases cathepsin L activity, thereby globally influencing neutrophil functionVenetta Thomas
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8031, USA
Infect Immun 76:4905-12. 2008..As therapeutic options for A. phagocytophilum and related organisms are limited, these results also identify a cellular pathway that may be targeted for the treatment of A. phagocytophilum infection...
Fucosylation enhances colonization of ticks by Anaplasma phagocytophilumJoao H F Pedra
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Cell Microbiol 12:1222-34. 2010..Our results uncover a novel mechanism of pathogen colonization in arthropods. Decoding mechanisms of pathogen invasion in ticks might expedite the development of new strategies to interfere with the life cycle of A. phagocytophilum...
Molecular adaptation of Borrelia burgdorferi in the murine hostFang Ting Liang
Section of Rheumatology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT 06520-8031, USA
J Exp Med 196:275-80. 2002..This novel adaptation mechanism could be a critical step for B. burgdorferi to proceed to chronic infection, as the pathogen would be cleared at the early stage of infection if the spirochetes failed to undergo this process...
Coinfection with Borrelia burgdorferi sensu stricto and Borrelia garinii alters the course of murine Lyme borreliosisJoppe W R Hovius
Section of Rheumatology, Department of Internal Medicine, Yale University, School of Medicine, New Haven, Connecticut, USA
FEMS Immunol Med Microbiol 49:224-34. 2007..Moreover, we suggest that competition of the two Borrelia species within the reservoir host could have led to preferential maintenance, and a rising prevalence, of B. burgdorferi sensu stricto in European I. ricinus populations...
Early transcriptional response of human neutrophils to Anaplasma phagocytophilum infectionBindu Sukumaran
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, The Anlyan Center for Medical Research and Education, New Haven, CT 06520-8031, USA
Infect Immun 73:8089-99. 2005..phagocytophilum-infected neutrophils and promyelocytic cell lines...
Protective niche for Borrelia burgdorferi to evade humoral immunityFang Ting Liang
Department of Internal Medicine, Section of Rheumatology, Yale University School of Medicine, New Haven, Connecticut, USA
Am J Pathol 165:977-85. 2004..These data suggest that spirochetal DbpA may interact with host decorin during infection and such interactions could be a mechanism that B. burgdorferi uses to evade humoral immunity and establish chronic infection...
Use of recombinant antigens of Borrelia burgdorferi and Anaplasma phagocytophilum in enzyme-linked immunosorbent assays to detect antibodies in white-tailed deerLouis A Magnarelli
Department of Entomology and Forestry and Horticulture, The Connecticut Agricultural Experiment Station, P O Box 1106, New Haven, Connecticut 06504, USA
J Wildl Dis 40:249-58. 2004..burgdorferi or A. phagocytophilum...
A comparison of serologic tests for the detection of serum antibodies to whole-cell and recombinant Borrelia burgdorferi antigens in cattleLouis A Magnarelli
Department of Entomology, The Connecticut Agricultural Experiment Station, P O Box 1106, New Haven, Connecticut 06504, USA
Can Vet J 45:667-73. 2004..Anaplasma marginale, or A. phagocytophilum were tested by ELISA with separate whole-cell or recombinant B. burgdorferi antigens. An ELISA and Western blot analyses can be used to confirm the exposure of cattle to B. burgdorferi...
Identification and characterization of Ixodes scapularis antigens that elicit tick immunity using yeast surface displayTim J Schuijt
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America
PLoS ONE 6:e15926. 2011..These studies also suggest that these antigens may serve as potential vaccine candidates to thwart tick feeding...
Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitisTian Wang
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06520, USA
Nat Med 10:1366-73. 2004..Collectively, WNV infection leads to a Tlr3-dependent inflammatory response, which is involved in brain penetration of the virus and neuronal injury...
Postgenomic analyses reveal development of infectious Anaplasma phagocytophilum during transmission from ticks to miceJuliana E Mastronunzio
Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA
J Bacteriol 194:2238-47. 2012..phagocytophilum during transmission from ticks to mammals and demonstrates that the abundantly expressed, DC-associated APH_1235 protein is important during in vivo infection by A. phagocytophilum...
Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderlyFeng Qian
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8031, USA
Aging Cell 11:104-10. 2012..Elevated TLR5 may provide a critical mechanism to enhance immune responsiveness in older individuals...
Inhibition of neutrophil function by two tick salivary proteinsXiuyang Guo
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8031, USA
Infect Immun 77:2320-9. 2009..Our results suggest that ISL 929 and ISL 1373 contribute to the inhibition of PMN functions shown previously with tick saliva and support important roles for these inhibitory proteins in the modulation of PMN function in vivo...
Borrelia burgdorferi lacking BBK32, a fibronectin-binding protein, retains full pathogenicityXin Li
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar St, New Haven, CT 06520-8031, USA
Infect Immun 74:3305-13. 2006..These results suggest that additional B. burgdorferi proteins can complement the function of BBK32, fibronectin binding or otherwise, during the natural spirochete life cycle...
Immunity against Ixodes scapularis salivary proteins expressed within 24 hours of attachment thwarts tick feeding and impairs Borrelia transmissionSukanya Narasimhan
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America
PLoS ONE 2:e451. 2007..Defining this subset of proteins will promote a mechanistic understanding of novel I. scapularis proteins critical for the initiation of tick feeding and for Borrelia transmission...
Use of RNA interference to prevent lethal murine west nile virus infectionFengwei Bai
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA
J Infect Dis 191:1148-54. 2005..These data show the efficacy of the prophylactic use of siRNAs against a viral infection in vivo and suggest new strategies to combat West Nile virus...
Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever virusesTonya M Colpitts
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America
PLoS Pathog 7:e1002189. 2011..This work provides an extensive list of targets for controlling flaviviral infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses...
Use of a tandem affinity purification assay to detect interactions between West Nile and dengue viral proteins and proteins of the mosquito vectorTonya M Colpitts
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
Virology 417:179-87. 2011..We show that the TAP method may be used in insect cells to accurately identify flaviviral-host protein interactions. Our data also provides several targets for interrupting flavivirus infection in mosquito vectors...
TLR9-targeted biodegradable nanoparticles as immunization vectors protect against West Nile encephalitisStacey L Demento
Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA
J Immunol 185:2989-97. 2010..Ultimately, compared with alum, this system offered superior protection in a mouse model of WN virus encephalitis...
A C-type lectin collaborates with a CD45 phosphatase homolog to facilitate West Nile virus infection of mosquitoesGong Cheng
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Cell 142:714-25. 2010..During the mosquito blood-feeding process, WNV infection was blocked in vivo with mosGCTL-1 antibodies. A molecular understanding of flaviviral-arthropod interactions may lead to strategies to control viral dissemination in nature...
A West Nile virus recombinant protein vaccine that coactivates innate and adaptive immunityWilliam F McDonald
VaxInnate Corporation, New Haven, CT 06511, USA
J Infect Dis 195:1607-17. 2007..They also support the further development of an effective WNV vaccine and novel monovalent and multivalent vaccines for related flaviviruses...
Anaplasma phagocytophilum modulates gp91phox gene expression through altered interferon regulatory factor 1 and PU.1 levels and binding of CCAAT displacement proteinVenetta Thomas
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, S525A, 300 Cedar St, P.O. Box 208031, New Haven, CT 06520-8031, USA
Infect Immun 73:208-18. 2005..phagocytophilum infection, providing evidence of the first molecular mechanism that a pathogen uses to alter the regulation of genes that contribute to an effective respiratory burst...
Human innate immunosenescence: causes and consequences for immunity in old ageAlexander Panda
Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA
Trends Immunol 30:325-33. 2009....
Crystal structure of west nile virus envelope glycoprotein reveals viral surface epitopesRyuta Kanai
266Department of Molecular Biophysics and Biochemistry, The Bass Center for Structural Biology, Yale University, 266 Whitney Ave, New Haven, Connecticut 06520, USA
J Virol 80:11000-8. 2006..By revealing the details of the molecular landscape of the West Nile virus surface, our structure will assist the design of antiviral vaccines and therapeutics...
RNA interference screen for human genes associated with West Nile virus infectionManoj N Krishnan
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticutt 06520 8031, USA
Nature 455:242-5. 2008..This study provides a comprehensive molecular portrait of WNV-human cell interactions that forms a model for understanding single plus-stranded RNA virus infection, and reveals potential antiviral targets...
Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasionAlvaro Arjona
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
J Clin Invest 117:3059-66. 2007....
Icam-1 participates in the entry of west nile virus into the central nervous systemJianfeng Dai
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, P O Box 208031, New Haven, CT 06520 8031, USA
J Virol 82:4164-8. 2008..These data suggest that ICAM-1 plays an important role in West Nile virus neuroinvasion and that targeting ICAM-1 signaling may help control viral encephalitis...
Passage through Ixodes scapularis ticks enhances the virulence of a weakly pathogenic isolate of Borrelia burgdorferiSarojini Adusumilli
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8031, USA
Infect Immun 78:138-44. 2010..These data suggest that transmission of a high-passage attenuated isolate of B. burgdorferi by the arthropod vector results in the generation of spirochetes that have enhanced pathogenesis in mice...
Disruption of Ixodes scapularis anticoagulation by using RNA interferenceSukanya Narasimhan
Sections of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 101:1141-6. 2004..These studies demonstrate that RNA interference can silence I. scapularis genes and disrupt their physiologic function in vivo, and they identify vaccine candidates that can alter vector engorgement...
Protective and therapeutic capacity of human single-chain Fv-Fc fusion proteins against West Nile virusL Hannah Gould
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA
J Virol 79:14606-13. 2005..These recombinant human scFvs are potential candidates for immunoprophylaxis and therapy of flavivirus infections...
Murine neutrophils require alpha1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilumJason A Carlyon
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520 8031, USA
Blood 102:3387-95. 2003..However, murine infection does not require neutrophil PSGL-1 expression, which has important implications for understanding how A phagocytophilum binds and infects neutrophils...
Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient miceLena Alexopoulou
Section of Immunobiology and The Howard Hughes Medical Institute, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
Nat Med 8:878-84. 2002..These data indicate that TLR1 and TLR2 are required for lipoprotein recognition and that defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to OspA vaccination...
Repression of rac2 mRNA expression by Anaplasma phagocytophila is essential to the inhibition of superoxide production and bacterial proliferationJason A Carlyon
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8031, USA
J Immunol 169:7009-18. 2002..These results directly attribute the inhibition of rac2 and gp91(phox) transcription to the loss of NADPH oxidase activity in A. phagocytophila-infected cells and demonstrate its importance to bacterial intracellular survival...
Increased TLR4 expression and downstream cytokine production in immunosuppressed adults compared to non-immunosuppressed adultsDana W Dunne
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America
PLoS ONE 5:e11343. 2010..We studied monocyte Toll-like receptor (TLR) expression and cytokine production in 137 patients with autoimmune diseases who were maintained on immunosuppressive medications and 419 non-immunosuppressed individuals...
Superoxide anion production during Anaplasma phagocytophila infectionTian Wang
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
J Infect Dis 186:274-80. 2002..phagocytophila infection. These data demonstrate respiratory burst inhibition by A. phagocytophila in vivo and on an individual cell basis by use of assays designed to evaluate CGD...
Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infectionVenetta Thomas
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Cell Microbiol 9:1730-7. 2007..These data demonstrate a role for A. phagocytophilum-mediated ROCK1 phosphorylation in infection, and suggests that inhibiting this pathway may lead to new, non-antibiotic strategies to treat human granulocytic anaplasmosis...
Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritisJuan Anguita
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
FEMS Immunol Med Microbiol 34:187-91. 2002..burgdorferi-specific antibody or cytokine responses. Cox-2 activity is therefore associated with the genesis of infectious arthritis caused by B. burgdorferi...
Examination of the Borrelia burgdorferi transcriptome in Ixodes scapularis during feedingSukanya Narasimhan
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, L Diagnostics, New Haven, Connecticut 06520, USA
J Bacteriol 184:3122-5. 2002..These data demonstrate a new approach to the global analysis of B. burgdorferi genes that are preferentially expressed within the vector during feeding...
An open-label, nonrandomized, single-center, prospective extension, clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer-surface protein A (OspA) Lyme disease vaccineRobert T Schoen
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
Clin Ther 25:210-24. 2003..An efficacy trial of an outer-surface protein A (OspA) Lyme disease vaccine demonstrated tolerability and efficacy against laboratory-confirmed Lyme disease after a primary series of 3 doses at 0, 1, and 12 months...
Invasion and survival strategies of Anaplasma phagocytophilumJason A Carlyon
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, Room 525A, 300 Cedar Street, New Haven, CT 06520-8031, USA
Cell Microbiol 5:743-54. 2003..This review focuses on some of the mechanisms that A. phagocytophilum uses for neutrophil adhesion, surviving within the hostile intracellular environment of its host neutrophil and for effectively disseminating to naïve host cells...
Seasonal prevalence of serum antibodies to whole cell and recombinant antigens of Borrelia burgdorferi and Anaplasma phagocytophilum in white-tailed deer in ConnecticutLouis A Magnarelli
Center for Vector Biology and Zoonotic Diseases, Departments of Entomology and Forestry and Horticulture, The Connecticut Agricultural Experiment Station, PO Box 1106, New Haven, CT 06504, USA
J Wildl Dis 46:781-90. 2010..November and December is a suitable period to obtain blood samples from deer to conduct serosurveillance for both bacteria...
Adaptation of Borrelia burgdorferi in the vector and vertebrate hostUtpal Pal
Room 525A, Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8031, USA
Microbes Infect 5:659-66. 2003..We also discuss the regulatory mechanisms linked with the development of molecular adaptation of spirochetes within different host environments...
Anaplasma phagocytophilum induces Ixodes scapularis ticks to express an antifreeze glycoprotein gene that enhances their survival in the coldGirish Neelakanta
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520 8022, USA
J Clin Invest 120:3179-90. 2010....
Interferon-gamma deficiency reveals that 129Sv mice are inherently more susceptible to Anaplasma phagocytophilum than C57BL/6 miceTian Wang
Section of Rheumatology, Department of Internal Medicine, Yale University of School of Medicine, 300 Cedar Street, New Haven, CT, USA
FEMS Immunol Med Microbiol 42:299-305. 2004..phagocytophilum than IFN-gamma deficient B6 mice. These data demonstrate that there is an inherent increased susceptibility of 129 mice, compared with B6 mice, to A. phagocytophilum that can only be discerned in the absence of IFN-gamma...
Modulation of NB4 promyelocytic leukemic cell machinery by Anaplasma phagocytophilumJoao H F Pedra
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, The Anlyan Center for Medical Research and Education, 300 Cedar St, Room 525A P.O. Box 208031, New Haven, CT 06520-8031, USA
Genomics 86:365-77. 2005..phagocytophilum infection and iron metabolism. Our study clearly demonstrates multifactorial effects of A. phagocytophilum infection on NB4 promyelocytic leukemic cell machinery...
DNA microarray assessment of putative Borrelia burgdorferi lipoprotein genesFang Ting Liang
Section of Rheumatology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut 06520-8031, USA
Infect Immun 70:3300-3. 2002..These data show that a DNA microarray can globally examine the genes encoding B. burgdorferi lipoproteins...
Anaplasma phagocytophilum utilizes multiple host evasion mechanisms to thwart NADPH oxidase-mediated killing during neutrophil infectionJason A Carlyon
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Infect Immun 72:4772-83. 2004..Once internalized, the bacterium resides within a protective vacuole that excludes p22(phox) and gp91(phox). Thus, A. phagocytophilum employs at least two strategies to protect itself from neutrophil NADPH oxidase-mediated killing...
A recombinant envelope protein-based enzyme-linked immunosorbent assay for West Nile virus serodiagnosisTian Wang
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8031, USA
Vector Borne Zoonotic Dis 2:105-9. 2002..Antibodies to the recombinant West Nile virus membrane and nonstructural 1 proteins were not detected in any of these sera. An E protein-based ELISA may aid in the serological diagnosis of West Nile virus infection...
Borrelia burgdorferi transcriptome in the central nervous system of non-human primatesSukanya Narasimhan
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 100:15953-8. 2003..burgdorferi gene expression in vivo. The results provide a global snapshot of the spirochetal transcriptome in the CNS and should spur the design of experiments aimed at understanding the molecular basis of neuroborreliosis...
Immunity to West Nile virusTian Wang
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Curr Opin Immunol 16:519-23. 2004..These efforts will facilitate the development of effective vaccines and therapies to combat WN virus...
Essential role for OspA/B in the life cycle of the Lyme disease spirocheteXiaofeng F Yang
Department of Microbiology, UT Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390-9048, USA
J Exp Med 199:641-8. 2004..However, OspA/B function was essential for Bb colonization of and survival within tick midguts, events crucial for sustaining Bb in its natural enzootic life cycle...
Tick-host-pathogen interactions in Lyme borreliosisJoppe W R Hovius
University of Amsterdam, Academic Medical Center, Center for Experimental and Molecular Medicine, 1105 AZ Amsterdam, The Netherlands
Trends Parasitol 23:434-8. 2007..Moreover, we discuss how such vector molecules could be used to develop vector-antigen-based vaccines to prevent the transmission of B. burgdorferi and, potentially, other arthropod-borne microbes...
Structurally distinct requirements for binding of P-selectin glycoprotein ligand-1 and sialyl Lewis x to Anaplasma phagocytophilum and P-selectinTadayuki Yago
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA
J Biol Chem 278:37987-97. 2003..phagocytophilum binds cooperatively to a nonsulfated N-terminal peptide in human PSGL-1 and to sLex expressed on PSGL-1 or other glycoproteins. Distinct bacterial adhesins may mediate these cooperative interactions...
Antibodies to granulocytic ehrlichiae in cattle from ConnecticutLouis A Magnarelli
Department of Entomology, Connecticut Agricultural Experiment Station, New Haven 06504, USA
J Med Microbiol 51:326-31. 2002..Different serological testing methods should be used to detect immunoglobulins...
Association of linear plasmid 28-1 with an arthritic phenotype of Borrelia burgdorferiQilong Xu
Department of Pathobiological Sciences, Louisiana State University, Skip Bertman Drive at River Road, Baton Rouge, LA 70803, USA
Infect Immun 73:7208-15. 2005..These pathogenicity studies associated lp28-1 with an arthritic phenotype and further studies may identify factors that contribute to arthritic pathology...
A differential role for BB0365 in the persistence of Borrelia burgdorferi in mice and ticksUtpal Pal
Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA
J Infect Dis 197:148-55. 2008..burgdorferi life cycle...
Differential expression of the p44 gene family in the agent of human granulocytic ehrlichiosisJacob W IJdo
Inflammation Program and Department of Internal Medicine, Veterans Administration Medical Center and University of Iowa, Iowa City 52242, USA
Infect Immun 70:5295-8. 2002..Similarly, the p44 genes were differentially expressed in infected C3H mice, in SCID mice, and in cultured HGE bacteria. Thus, differential p44 expression exists in vivo and in vitro and could provide a basis for antigenic variation...
Research Grants
- BORRELIA BURGDORFERI INTERACTIONS WITH IXODES SCAPULARISErol Fikrig; Fiscal Year: 2010..If successful, these studies may lead to new strategies for the prevention of B. burgdorferi infection. This paradigm would also be applicable to other vector-borne pathogens of medical importance. ..
- Tissue Specific Borrelia Gene ExpessionErol Fikrig; Fiscal Year: 2005....
- Toll-like receptor responses to West Nile virusErol Fikrig; Fiscal Year: 2007..These studies should increase our understanding of the role of TLR3 in viral recognition, and may lead to new strategies to prevent, or treat, WN virus infection. ..
- Tissue-specific Borrelia Gene ExpressionErol Fikrig; Fiscal Year: 2007..These data will lead to a greater understanding of how tissue-specific B. burgdorferi gene expression contributes to spirochete survival, and suggest new strategies for the prevention and/or treatment of Lyme disease. ..
- BORRELIA BURGDORFERI INTERACTIONS WITH IXODES SCAPULARISErol Fikrig; Fiscal Year: 2007..burgdorferi and I. scapularis - with an emphasis on OspA and TROSPA - leading to a greater appreciation of the B. burgdorferi lifecycle and new approaches to interfere with spirochete transmission. ..
- Interactions Between Anaplasma Phagocytophilum and Ixodes ScapularisErol Fikrig; Fiscal Year: 2010..phagocytophilum pathogenesis and may suggest new ways to prevent infection. It is also hopeful that these paradigms would also be applicable to other vector-borne pathogens of medical importance. ..
- Immunotherapeutics for Treatment of Flavivirus InfectionErol Fikrig; Fiscal Year: 2007..The recombinant antibodies will be fully human, produced rapidly and in high titer, free of blood-borne pathogens, and will be promising candidates for further development as a clinical reagent to combat flaviviral infection. ..
- IMMUNOPATHOGENESIS OF GRANULOCYTIC EHRLICHIOSISErol Fikrig; Fiscal Year: 2007..These studies should lead to a greater understanding of HGE, an important new tick-borne disease, and the mechanisms that pathogens may use to interfere with neutrophil function. ..
- Neutrophil gene expression induced by A. phagocytophilaErol Fikrig; Fiscal Year: 2004..phagocytophila uses to interfere with neutrophil differentiation and function ..
- ARTHROPOD SPECIFIC BORRELIA BURGDORFERI GENE EXPRESSIONErol Fikrig; Fiscal Year: 2002..burgdorferi gene expression in ticks, spirochete transmission from the vector, and the role of antibodies in the destruction of B. burgdorferi throughout its complete lifecycle in the vector. ..
- IMMUNOPATHOGENESIS OF GRANULOCYTIC EHRLICHIOSISErol Fikrig; Fiscal Year: 2002..The development and characterization of a murine model of HGE, including the HGE-specific host immune response to infection, will further our understanding of this disease, and provide information on host immunity to infection. ..
