Immunology and Infectious Disease Commons^™

A Draft Of The Genome Of The Gulf Coast Tick, Amblyomma Maculatum, Jose M.C. Ribeiro, Natalia J. Bayona-Vásquez, Khemraj Budachetri, Deepak Kumar, Julia Catherine Frederick, Faizan Tahir, Brant C. Faircloth, Travis C. Glenn, Shahid Karim

Faculty Publications

The Gulf Coast tick, Amblyomma maculatum, inhabits the Southeastern states of the USA bordering the Gulf of Mexico, Mexico, and other Central and South American countries. More recently, its U.S. range has extended West to Arizona and Northeast to New York state and Connecticut. It is a vector of Rickettsia parkeri and Hepatozoon americanum. This tick species has become a model to study tick/Rickettsia interactions. To increase our knowledge of the basic biology of A. maculatum we report here a draft genome of this tick and an extensive functional classification of its proteome. The DNA from a single …

Robust Network Stability Of Mosquitoes And Human Pathogens Of Medical Importance, Donald A. Yee, Catherine Dean Bermond, Limarie J. Reyes-Torres, Nicole S. Fijman, Nicole A. Scavo, Joseph Nelsen, Susan H. Yee

Faculty Publications

Background: The exact number of mosquito species relevant to human health is unknown, posing challenges in understanding the scope and breadth of vector–pathogen relationships, and how resilient mosquito vector–pathogen networks are to targeted eradication of vectors.

Methods: We performed an extensive literature survey to determine the associations between mosquito species and their associated pathogens of human medical importance. For each vector–pathogen association, we then determined the strength of the associations (i.e., natural infection, lab infection, lab dissemination, lab transmission, known vector). A network analysis was used to identify relationships among all pathogens and vectors. Finally, we examined how …

An Exploratory Study On The Microbiome Of Northern And Southern Populations Of Ixodes Scapularis Ticks Predicts Changes And Unique Bacterial Interactions, Deepak Kumar, Latoyia P. Downs, Abdulsalam Adegoke, Erika Machtinger, Kelly Oggenfuss, Richard S. Ostfeld, Monica Embers, Shahid Karim

Faculty Publications

The black-legged tick (Ixodes scapularis) is the primary vector of Borrelia burgdorferi, the causative agent of Lyme disease in North America. However, the prevalence of Lyme borreliosis is clustered around the Northern States of the United States of America. This study utilized a metagenomic sequencing approach to compare the microbial communities residing within Ix. scapularis populations from northern and southern geographic locations in the USA. Using a SparCC network construction model, we performed potential interactions between members of the microbial communities from Borrelia burgdorferi–infected tissues of unfed and blood-fed ticks. A significant difference in bacterial composition …

Tick Salivary Gland Extract Induces Alpha-Gal Syndrome In Alpha-Gal Deficient Mice, Shailesh K. Choudhary, Shahid Karim, Onyinye I. Iweala, Shivangi Choudhary, Gary Crispell, Surendra Raj Sharma, Claire T. Addison, Mike Kulis, Brian H. Herrin, Susan E. Little, Scott P. Commins

Faculty Publications

Introduction: Alpha-gal syndrome (AGS) is characterized by delayed hypersensitivity to non-primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose-alpha-1,3-galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U.S. A small animal model of meat allergy is needed to study the mechanism of alpha-gal sensitization, the effector phase leading to delayed allergic responses and potential therapeutics to treat AGS.

Methods: Eight- to ten-weeks old mice with a targeted inactivation of alpha-1,3-galactosyltransferase (AGKO) were injected intradermally with 50 μg of Aa tick salivary gland extract (TSGE) on days …

Tick Saliva And The Alpha-Gal Syndrome: Finding A Needle In A Haystack, Surendra Raj Sharma, Shahid Karim

Faculty Publications

Ticks and tick-borne diseases are significant public health concerns. Bioactive molecules in tick saliva facilitate prolonged blood-feeding and transmission of tick-borne pathogens to the vertebrate host. Alpha-gal syndrome (AGS), a newly reported food allergy, is believed to be induced by saliva proteins decorated with a sugar molecule, the oligosaccharide galactose-⍺-1,3-galactose (α-gal). This syndrome is characterized by an IgE antibody-directed hypersensitivity against α-gal. The α-gal antigen was discovered in the salivary glands and saliva of various tick species including, the Lone Star tick (Amblyomma americanum). The underlying immune mechanisms linking tick bites with α-gal-specific IgE production are poorly understood and are …

Recent Advances In Understanding Tick And Rickettsiae Interactions, Shahid Karim, Deepak Kumar, Khemraj Budachetri

Faculty Publications

Ticks are haematophagous arthropods with unique molecular mechanisms for digesting host blood meal while acting as vectors for various pathogens of public health significance. The tick's pharmacologically active saliva plays a fundamental role in modulating the host's immune system for several days to weeks, depending on the tick species. The vector tick has also developed sophisticated molecular mechanisms to serve as a competent vector for pathogens, including the spotted fever group (SFG) rickettsiae. Evidence is still inadequate concerning tick–rickettsiae–host interactions and saliva-assisted transmission of the pathogen to the mammalian host. Rickettsia parkeri, of the SFG rickettsia, can cause a …

Interleukin-17a Facilitates Chikungunya Virus Infection By Inhibiting Ifn-Α2 Expression, Biswas Neupane, Dhiraj Acharya, Farzana Nazneen, Gabriel Gonzalez-Fernandez, Alex Sutton Flynt, Fengwei Bai

Faculty Publications

Interferons (IFNs) are the key components of innate immunity and are crucial for host defense against viral infections. Here, we report a novel role of interleukin-17A (IL-17A) in inhibiting IFN-α2 expression thus promoting chikungunya virus (CHIKV) infection. CHIKV infected IL-17A deficient (Il17a^−/−) mice expressed a higher level of IFN-α2 and developed diminished viremia and milder footpad swelling in comparison to wild-type (WT) control mice, which was also recapitulated in IL-17A receptor-deficient (Il17ra^−/−) mice. Interestingly, IL-17A selectively blocked IFN-α2 production during CHIKV, but not West Nile virus (WNV) or Zika virus (ZIKV), infections. Recombinant IL-17A …

Laboratory Colonization By Dirofilaria Immitis Alters The Microbiome Of Female Aedes Aegypti Mosquitoes, Abdulsalam Adegoke, Erik Neff, Amie Geary, Montana Ciara Husser, Kevin Wilson, Shawn Michael Norris, Guha Dharmarajan, Shahid Karim

Faculty Publications

Background

The ability of blood-feeding arthropods to successfully acquire and transmit pathogens of medical and veterinary importance has been shown to be interfered with, or enhanced by, the arthropod’s native microbiome. Mosquitoes transmit viruses, protozoan and filarial nematodes, the majority of which contribute to the 17% of infectious disease cases worldwide. Dirofilaria immitis, a mosquito-transmitted filarial nematodes of dogs and cats, is vectored by several mosquito species including Aedes aegypti.

Methods

In this study, we investigated the impact of D. immitis colonization on the microbiome of laboratory reared female Ae. aegypti. Metagenomic analysis of the V3–V4 variable …

Tumor Necrosis Factor-Alpha Signaling May Contribute To Chronic West Nile Virus Post-Infectious Proinflammatory State, A. Arturo Leis, Marie F. Grill, Brent P. Goodman, Syed B. Sadiq, David J. Sinclair, Parminder J.S. Vig, Fengwei Bai

Faculty Publications

Background: West Nile virus (WNV) causes a spectrum of human disease ranging from a febrile illness (WNV fever) to severe neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis). Since WNV gained entry into North America in 1999, clinicians caring for WNV survivors have observed persistent neurological symptoms occurring long-after the production of neutralizing antibodies and clearance of the virus. Accordingly, alternative pathogeneses other than direct viral invasion have been hypothesized to explain these post-infectious symptoms. The dominant hypothesis is that antiviral inflammatory responses triggered initially to clear WNV may persist to promote a post-infectious proinflammatory state.

Methods: In 4 serologically-confirmed …

Defining Parental Resistance: The Social Determinants Of Measles Vaccine Hesitancy, Michael C. Goates, M. Lelinneth B. Novilla, Mallory Showalter, L. Kirsten Novilla, Russell Doria, Michael Dang, Tyler Leffler, Katelyn Aldridge

Faculty Publications

The increase in vaccine-preventable disease (VPD) outbreaks has caused great alarm to the public health community. In recent years, VPD outbreaks have occurred across the globe in both developed and developing countries. Particularly troubling has been the resurgence of diseases formerly eradicated through years of concerted vaccination and other public health campaigns. Higher vaccination exemption rates have been implicated in the resurgence of VPDs. This is particularly evident in the United States where measles outbreaks reached 1,250 individual cases in 2019 alone, the most confirmed cases since 1992. Central to the discussion about measles resurgence is a better understanding of …

Cysteine Dioxygenase Enzyme Activity And Gene Expression In The Dimorphic Pathogenic Fungus Histoplasma Capsulatum Is In Both The Mold And Yeast Morphotypes And Exhibits Substantial Strain Variation, Melissa Adams, Glen Shearer

Faculty Publications

In the dimorphism (mold/yeast) Histoplasma capsulatum (Hc) literature are reports that yeast (the so-called pathogenic form) uniquely expresses a cysteine dioxygenase (CDO, approx. 10,500 dal) activity which the mold morphotype (the so-called saprophytic soil form) does not express (C.F., Kumar et al., Biochem 22, 762, 1983). This yeast-specific CDO activity is postulated to play a critical role in the mold-to-yeast shift. A number of years ago, our lab isolated the gene encoding the Hc cysteine dioxygenase (CDO1, Genbank accession AY804144) and noted significant expression in the mold morphotype of several Histoplasma strains and also determined that the predicted protein would …

Phylogenetic Afficity Of Genolopa (Digenea: Monorchiidae) With Descriptions Of Two New Species, Apryle J. Panyi, Stephen S. Curran, Robin M. Overstreet

Faculty Publications

The validity of Genolopa Linton, 1910 has been controversial because the observation of presently recognized critical diagnostic morphological features (spines in the genital atrium and a bipartite, anteriorly spined terminal organ) were omitted from the original diagnosis, and these features were not universally appreciated as important diagnostic features until 2008. Modern taxonomists have been further challenged by inappropriate fixation techniques that have resulted in various interpretations of morphological features. Consequently, named species in the genus have fluctuated among other monorchiid genera depending on various interpretations by taxonomists, and a modern consensus on classifying these species is lacking. This study …

The Impact Of Msaabcr On Sara-Associated Phenotypes Is Different In Divergent Clinical Isolates Of Staphylococcus Aureus, Joseph S. Rom, Aura M. Ramirez, Karen E. Beenken, Gyan S. Sahukhal, Mohamed O. Elasri, Mark S. Smeltzer

Faculty Publications

The staphylococcal accessory regulator (sarA) plays an important role in Staphylococcus aureus infections including osteomyelitis, and the msaABCR operon has been implicated as an important factor in modulating expression of sarA. Thus, we investigated the contribution of msaABCR to sarA-associated phenotypes in the S. aureus clinical isolates LAC and UAMS-1. Mutation of msaABCR resulted in reduced production of SarA and a reduced capacity to form a biofilm in both strains. Biofilm formation was enhanced in a LAC msa mutant by restoring the production of SarA, but this was not true in a UAMS-1 msa mutant. Similarly, …

Structural And Functional Determinants Of Rodent And Human Surfactant Protein A: A Synthesis Of Binding And Computational Data, Armen Nalian, Todd M. Umstead, Ching-Hui Yang, Patricia Silveyra, Neal J. Thomas, Joanna Floros, Francis X. Mccormack, Zissis C. Chroneos

Faculty Publications

Surfactant protein A (SP-A) provides surfactant stability, first line host defense, and lung homeostasis by binding surfactant phospholipids, pathogens, alveolar macrophages (AMs), and epithelial cells. Non-primates express one SP-A protein whereas humans express two: SP-A1 and SP-A2 with core intra- and inter-species differences in the collagen-like domain. Here, we used macrophages and solid phase binding assays to discern structural correlates of rat (r) and human (h) SP-A function. Binding assays using recombinant rSP-A expressed in insect cells showed that lack of proline hydroxylation, truncations of amino-terminal oligomerization domains, and site-directed serine (S) or alanine (A) mutagenesis of cysteine 6 (C6S), …

Differential Expression Of Genes Related To Innate Immune Responses In Ex Vivo Spinal Cord And Cerebellar Slice Cultures Infected With West Nile Virus, Parminder J.S. Vig, Deyin Lu, Amber M. Paul, Ram Kuwar, Maria Lopez, Dobrivoje S. Stokic, A. Arturo Leis, Michael R. Garrett, Fengwei Bai

Faculty Publications

West Nile virus (WNV) infection results in a spectrum of neurological symptoms, ranging from a benign fever to severe WNV neuroinvasive disease with high mortality. Many who recover from WNV neuroinvasive infection present with long-term deficits, including weakness, fatigue, and cognitive problems. While neurons are a main target of WNV, other cell types, especially astrocytes, play an important role in promoting WNV-mediated central nervous system (CNS) damage. Conversely, it has been shown that cultured primary astrocytes secrete high levels of interferons (IFNs) immediately after WNV exposure to protect neighboring astrocytes, as well as neurons. However, how intrinsic responses to WNV …

An Expanded Toolkit For Gene Tagging Based On Mimic And Scarless Crispr Tagging In, David Li-Kroeger, Oguz Kanca, Pei-Tseng Lee, Sierra Cowan, Michael T Lee, Manish Jaiswal, Jose Luis Salazar, Yuchun He, Zhongyuan Zuo, Hugo J Bellen

Faculty Publications

We generated two new genetic tools to efficiently tag genes in Drosophila. The first, Double Header (DH) utilizes intronic MiMIC/CRIMIC insertions to generate artificial exons for GFP mediated protein trapping or T2A-GAL4 gene trapping in vivo based on Cre recombinase to avoid embryo injections. DH significantly increases integration efficiency compared to previous strategies and faithfully reports the expression pattern of genes and proteins. The second technique targets genes lacking coding introns using a two-step cassette exchange. First, we replace the endogenous gene with an excisable compact dominant marker using CRISPR making a null allele. Second, the insertion is replaced …

A Time Course Study Of Rotavirus-Infected Intestinal Cells Treated With Stilbenoids And The Regulation Of Apoptosis, Rebecca D. Parr, Caleb M. Witcher, Rebekah Napier-Jameson, Hannah L. Wilson, Stormey Wisdom, Macie N. Mattila, Essence B. Strange, Josephine Taylor, Beatrice Clack, Fabricio Medina-Bolivar, Judith M. Ball

Faculty Publications

This is a time course study of virus –host interactions that are modified with the addition of two small natural products. They appear to effect virus replication and the host response to the infection.

A Rare Case Of Erythema Elevatum Diutinum Presenting As Diffuse Neuropathy., G H. Nguyen, E L. Guo, D Norris

Faculty Publications

no abstract available

Influence Of Maternal Breast Milk Ingestion On Acquisition Of The Intestinal Microbiome In Preterm Infants., Katherine E Gregory, Buck S Samuel, Pearl Houghteling, Guru Shan, Frederick M Ausubel, Ruslan I Sadreyev, W Allan Walker

Faculty Publications

BACKGROUND: The initial acquisition and early development of the intestinal microbiome during infancy are important to human health across the lifespan. Mode of birth, antibiotic administration, environment of care, and nutrition have all been shown to play a role in the assembly of the intestinal microbiome during early life. For preterm infants, who are disproportionately at risk of inflammatory intestinal disease (i.e., necrotizing enterocolitis), a unique set of clinical factors influence the establishment of the microbiome. The purpose of this study was to establish the influence of nutritional exposures on the intestinal microbiome in a cohort of preterm infants early …

Consensus Paper: Cerebellar Development., K Leto, M Arancillo, Ebe Becker, A Chiang, Et Al.

Faculty Publications

The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.

Calling In Sick: Impacts Of Fever On Intra-Urban Human Mobility, T. Alex Perkins, Valerie A. Paz-Soldan, Steven T. Stoddard, Amy C. Morrison, Brett M. Forshey, Kanya C. Long, Eric S. Halsey, Tadeusz J. Kochel, John P. Elder, Uriel Kitron, Thomas W. Scott, Gonzalo M. Vazquez-Prokopec

Faculty Publications

© 2016 The Author(s) Published by the Royal Society. All rights reserved. Pathogens inflict a wide variety of disease manifestations on their hosts, yet the impacts of disease on the behaviour of infected hosts are rarely studied empirically and are seldom accounted for in mathematical models of transmission dynamics. We explored the potential impacts of one of the most common disease manifestations, fever, on a key determinant of pathogen transmission, host mobility, in residents of the Amazonian city of Iquitos, Peru. We did so by comparing two groups of febrile individuals (dengue-positive and dengue-negative) with an afebrile control group. A …

Comparison Of Interactive Voice Response (Ivr) With Paper Administration Of Instruments To Assess Functional Status, Sexual Function, And Quality Of Life In Elderly Men., Rc Rosen, Aj Stephens-Shields, Gr Cunningham, D Cifelli, D Cella, Jt Farrar, E Barrett-Connor, Ce Lewis, M Pahor, X Hou, Pj Snyder

Faculty Publications

PURPOSE: Patient-reported outcome (PRO) measures are essential for assessing subjective patient experiences. Interactive voice response (IVR) data collection provides advantages for clinical trial design by standardizing and centralizing the assessment. Prior to adoption of IVR as a mode of PRO administration in the Testosterone Trials (TTrials), we compared IVR to paper versions of the instruments to be used. METHODS: IVR versions of the FACIT-Fatigue scale and Psychosexual Daily Questionnaire, Question 4, were developed. In one pilot study, IVR versions of these scales were compared to paper versions in 25 men = 65 years at each of two clinical sites. In …

Ct-Based Structural Rigidity Analysis Is More Accurate Than Mirels Scoring For Fracture Prediction In Metastatic Femoral Lesions., Ta Damron, A Nazarian, V Entezari, C Brown, W Grant, N Calderon, Et Al.

Faculty Publications

BACKGROUND: Controversy continues regarding the appropriate assessment of fracture risk in long bone lesions affected by disseminated malignancy. QUESTIONS/PURPOSES: The purpose of this ongoing Musculoskeletal Tumor Society-sponsored, multi-institutional prospective cross-sectional clinical study is to compare CT-based structural rigidity analysis (CTRA) with physician-derived Mirels scoring for predicting pathologic fracture in femoral bone lesions. We hypothesized CTRA would be superior to Mirels in predicting fracture risk within the first year based on (1) sensitivity, specificity, positive predictive value, and negative predictive value; (2) receiver operator characteristic (ROC) analysis; and (3) fracture prediction after controlling for potential confounding variables such as age and …

Explicit Time Deficit In Schizophrenia: Systematic Review And Meta-Analysis Indicate It Is Primary And Not Domain Specific., V Ciullo, G Spalletta, C Caltagirone, Re Jorge, F Piras

Faculty Publications

Although timing deficits are a robust finding in schizophrenia (SZ), the notion of a genuine time perception disorder in SZ is still being debated because distortions in timing might depend on neuropsychological deficits that are characteristics of the illness. Here we used meta-analytic methods to summarize the evidence of timing deficits in SZ and moderator analyses to determine whether defective timing in SZ arises from nontemporal sources or from defective time perception. PubMed Services, PsycNET, and Scopus were searched through March 2015, and all references in articles were investigated to find other relevant studies. Studies were selected if they included …

Incomplete Protection Against Dengue Virus Type 2 Re-Infection In Peru, Brett M. Forshey, Robert C. Reiner, Sandra Olkowski, Amy C. Morrison, Angelica Espinoza, Kanya C. Long, Stalin Vilcarromero, Wilma Casanova, Helen J. Wearing, Eric S. Halsey, Tadeusz J. Kochel, Thomas W. Scott, Steven T. Stoddard

Faculty Publications

© 2016 Public Library of Science. All Rights Reserved. Background: Nearly half of the world’s population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010–2011, 15 years after the first outbreak of DENV-2 in the region. Methodology/Principal Findings: We estimated the age-dependent prevalence …

Early Rescue Of Interneuron Disease Trajectory In Developmental Epilepsies., Ms Siehr, Jl Noebels

Faculty Publications

The discovery of over 150 monogenic epilepsies and advances in early genetic diagnoses have launched a search for molecular strategies and developmental timetables to reverse or even prevent the course of these debilitating brain disorders. Orthologous rodent models of key disease genes are providing important examples of the range of targets, and serve as valuable test systems for perinatal therapeutic approaches. While gene-specific analyses of single rare 'orphan' diseases are each narrow in scope, they illuminate downstream pathways converging onto interneurons, and treatments that strengthen inhibition during cortical maturation may provide broad protection against these seemingly disparate gene errors. Several …

Efficacy Of Psychosocial Interventions In Inducing And Maintaining Alcohol Abstinence In Patients With Chronic Liver Disease: A Systematic Review., A Khan, A Tansel, Dl White, Wt Kayani, Wt Bano, J Lindsay, Hb El-Serag, F Kanwal

Faculty Publications

BACKGROUND & AIMS: We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). METHODS: We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. RESULTS: We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), …

Eosinophilic Esophagitis In Children And Its Relationship With Parental Allergies: Texas Children's Hospital Experience., G Hiremath, D Byramji, A Pacheco, G Constantine, C Davis, R Shulman, A Olive

Faculty Publications

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergen-mediated, clinicopathological condition affecting all ages. The characteristics of children with EoE in the southwestern USA have not been fully described. Furthermore, very little is known about the relationship between parental allergies and risk of EoE in their offspring in this patient population. AIMS: To characterize children with EoE and to examine the relationship between prevalence of parental allergies and occurrence of EoE in their offspring at a single referral pediatric center in the southwestern USA. METHODS: Demographic and clinical information of 126 children (=18 years of age) with EoE was abstracted in a …

Glial Contributions To Neural Function And Disease., Mn Rasband

Faculty Publications

The nervous system consists of neurons and glial cells. Neurons generate and propagate electrical and chemical signals, whereas glia function mainly to modulate neuron function and signaling. Just as there are many different kinds of neurons with different roles, there are also many types of glia that perform diverse functions. For example, glia make myelin; modulate synapse formation, function, and elimination; regulate blood flow and metabolism; and maintain ionic and water homeostasis to name only a few. Although proteomic approaches have been used extensively to understand neurons, the same cannot be said for glia. Importantly, like neurons, glial cells have …

Effect Of Two-Year Caloric Restriction On Bone Metabolism And Bone Mineral Density In Non-Obese Younger Adults: A Randomized Clinical Trial., Dt Villareal, L Fontana, Sk Das, Et Al.

Faculty Publications

Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1?±?1.7?kg/m(2) ), younger (age 37.9?±?7.2 years) adults were randomly assigned to 25% CR (CR group, n?=?143) or ad libitum (AL group, n?=?75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (-7.5?±?0.4 versus …