Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Kulcsar M[original query] |
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Asymptomatic Infection of Marburg Virus Reservoir Bats Is Explained by a Strategy of Immunoprotective Disease Tolerance.
Guito JC , Prescott JB , Arnold CE , Amman BR , Schuh AJ , Spengler JR , Sealy TK , Harmon JR , Coleman-McCray JD , Kulcsar KA , Nagle ER , Kumar R , Palacios GF , Sanchez-Lockhart M , Towner JS . Curr Biol 2020 31 (2) 257-270 e5 Marburg virus (MARV) is among the most virulent pathogens of primates, including humans. Contributors to severe MARV disease include immune response suppression and inflammatory gene dysregulation ("cytokine storm"), leading to systemic damage and often death. Conversely, MARV causes little to no clinical disease in its reservoir host, the Egyptian rousette bat (ERB). Previous genomic and in vitro data suggest that a tolerant ERB immune response may underlie MARV avirulence, but no significant examination of this response in vivo yet exists. Here, using colony-bred ERBs inoculated with a bat isolate of MARV, we use species-specific antibodies and an immune gene probe array (NanoString) to temporally characterize the transcriptional host response at sites of MARV replication relevant to primate pathogenesis and immunity, including CD14(+) monocytes/macrophages, critical immune response mediators, primary MARV targets, and skin at the inoculation site, where highest viral loads and initial engagement of antiviral defenses are expected. Our analysis shows that ERBs upregulate canonical antiviral genes typical of mammalian systems, such as ISG15, IFIT1, and OAS3, yet demonstrate a remarkable lack of significant induction of proinflammatory genes classically implicated in primate filoviral pathogenesis, including CCL8, FAS, and IL6. Together, these findings offer the first in vivo functional evidence for disease tolerance as an immunological mechanism by which the bat reservoir asymptomatically hosts MARV. More broadly, these data highlight factors determining disparate outcomes between reservoir and spillover hosts and defensive strategies likely utilized by bat hosts of other emerging pathogens, knowledge that may guide development of effective antiviral therapies. |
The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity.
Pavlovich SS , Lovett SP , Koroleva G , Guito JC , Arnold CE , Nagle ER , Kulcsar K , Lee A , Thibaud-Nissen F , Hume AJ , Muhlberger E , Uebelhoer LS , Towner JS , Rabadan R , Sanchez-Lockhart M , Kepler TB , Palacios G . Cell 2018 173 (5) 1098-1110 e18 Bats harbor many viruses asymptomatically, including several notorious for causing extreme virulence in humans. To identify differences between antiviral mechanisms in humans and bats, we sequenced, assembled, and analyzed the genome of Rousettus aegyptiacus, a natural reservoir of Marburg virus and the only known reservoir for any filovirus. We found an expanded and diversified KLRC/KLRD family of natural killer cell receptors, MHC class I genes, and type I interferons, which dramatically differ from their functional counterparts in other mammals. Such concerted evolution of key components of bat immunity is strongly suggestive of novel modes of antiviral defense. An evaluation of the theoretical function of these genes suggests that an inhibitory immune state may exist in bats. Based on our findings, we hypothesize that tolerance of viral infection, rather than enhanced potency of antiviral defenses, may be a key mechanism by which bats asymptomatically host viruses that are pathogenic in humans. |
De novo transcriptome reconstruction and annotation of the Egyptian rousette bat.
Lee AK , Kulcsar KA , Elliott O , Khiabanian H , Nagle ER , Jones ME , Amman BR , Sanchez-Lockhart M , Towner JS , Palacios G , Rabadan R . BMC Genomics 2015 16 1033 BACKGROUND: The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. With Ebola virus, Marburg virus is a member of the family Filoviridae that causes severe hemorrhagic fever disease in humans and nonhuman primates, but results in little to no pathological consequences in bats. Understanding host-pathogen interactions within reservoir host species and how it differs from hosts that experience severe disease is an important aspect of evaluating viral pathogenesis and developing novel therapeutics and methods of prevention. RESULTS: Progress in studying bat reservoir host responses to virus infection is hampered by the lack of host-specific reagents required for immunological studies. In order to establish a basis for the design of reagents, we sequenced, assembled, and annotated the R. aegyptiacus transcriptome. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. We observed high similarity between this transcriptome and those available from other bat species. Gene expression analysis demonstrated clustering of expression profiles by tissue, where we also identified enrichment of tissue-specific gene ontology terms. In addition, we identified and experimentally validated the expression of novel coding transcripts that may be specific to this species. CONCLUSION: We comprehensively characterized the R. aegyptiacus transcriptome de novo. This transcriptome will be an important resource for understanding bat immunology, physiology, disease pathogenesis, and virus transmission. |
Improving stroke outcomes in rural areas through telestroke programs: an examination of barriers, facilitators, and state policies
Kulcsar M , Gilchrist S , George MG . Telemed J E Health 2014 20 (1) 3-10 INTRODUCTION: Every year in the United States more than 600,000 ischemic stroke patients do not receive proven, effective stroke treatment or may not be medically eligible to receive the one medication endorsed by the U.S. Food and Drug Administration for acute ischemic stroke. The lack of treatment is due partly to shortages of neurological experts in rural and underserved areas. Telestroke programs can improve stroke care for stroke patients in rural and underserved settings by using interactive telecommunication technology that connects centrally located neurological experts to rural healthcare facilities. Many states have enacted policies and practices that facilitate telestroke access. MATERIALS AND METHODS: We reviewed statutes and regulations in all 50 states that affect the adoption of telemedicine programs and describe examples of state-implemented programs in two states with policies that encourage telestroke use. RESULTS AND DISCUSSION: This review presents evidence of the value and effectiveness of telestroke programs, as well as an explanation of common barriers and facilitators of telestroke, including licensing and credentialing rules, reimbursement issues, and liability concerns. Most states have adopted policies that affect the adoption of telestroke programs. Georgia and South Carolina are examples of states implementing stroke policies using a telestroke model to treat stroke patients in rural areas. |
News from the CDC: integrating behavioral health into the patient-centered medical home
Chowdhury F , Kulcsar M , Gilchrist S , Hawkins N . Transl Behav Med 2012 2 (3) 257-259 Persons with mental illness are at higher risk of developing life-threatening physical conditions or dying prematurely [1], and several studies have reported improvements in health status when patients received integrated services. By integrating behavioral health services with primary care services, we can improve health care quality, preventive care practices, and health outcomes and reduce fragmented health care delivery for people who have mental illness or addictions and physical health problems [2, 3]. An emerging model for improving health care quality in the USA is the patient-centered medical home (PCMH). This model may provide an ideal way to integrate behavioral health and primary care services [4], particularly for persons with chronic conditions such as diabetes [5, 6] and hypertension [7, 8]. Already, some federal programs and state policies are supporting this approach as a way to integrate and improve health care services for persons with behavioral and physical health problems. |
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