A5017568330- Viral-associated cancers and disorders
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- Respiratory viral infections research
- Parvovirus B19 Infection Studies
- Animal Virus Infections Studies
- COVID-19 epidemiological studies
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- SARS-CoV-2 detection and testing
- Histiocytic Disorders and Treatments
- Viral Infections and Outbreaks Research
- Pediatric Hepatobiliary Diseases and Treatments
- Polyomavirus and related diseases
- Kawasaki Disease and Coronary Complications
- Immunotherapy and Immune Responses
- Heat shock proteins research
- Vaccine Coverage and Hesitancy
- Eosinophilic Disorders and Syndromes
- Cell Adhesion Molecules Research
University of Arkansas for Medical Sciences
2015-2025
Winthrop Rockefeller Foundation
2019-2024
Emory University
2007-2010
Vanderbilt University
2001-2006
Harvard University
2003
Massachusetts General Hospital
2003
Background Activation of the immune system is implicated in Post-Acute Sequelae after SARS-CoV-2 infection (PASC) but mechanisms remain unknown. Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin II (Ang II) resulting decreased activation AT1 receptor and activation. We hypothesized that autoantibodies against ACE2 may develop infection, as anti-idiotypic antibodies to anti-spike protein antibodies. Methods findings tested plasma or serum for 67 patients with known 13 no history...
Many serotype 3 reoviruses bind to two different host cell molecules, sialic acid and an unidentified protein, using discrete receptor-binding domains in viral attachment ς1. To determine mechanisms by which these events cooperate mediate attachment, we generated isogenic reovirus strains that differ the capacity acid. Strain SA+, but not SA−, bound specifically on a biosensor chip with nanomolar avidity. SA+ displayed 5-fold higher avidity for HeLa cells when compared although both...
ABSTRACT Reovirus infection is initiated by interactions between the attachment protein σ1 and cell surface carbohydrate junctional adhesion molecule A (JAM-A). Expression of a JAM-A mutant lacking cytoplasmic tail in nonpermissive cells conferred full susceptibility to reovirus infection, suggesting that molecules other than mediate viral internalization following attachment. The presence integrin-binding sequences outer capsid λ2, which serves as structural base for σ1, suggests integrins...
Reovirus attachment to cells is mediated by the binding of viral protein σ1 junctional adhesion molecule 1 (JAM1). The crystal structure extracellular region human JAM1 (hJAM1) reveals two concatenated Ig-type domains with a pronounced bend at domain interface. Two hJAM1 molecules form dimer that stabilized extensive ionic and hydrophobic contacts between N-terminal domains. This dimeric arrangement similar observed previously in murine homolog JAM1, indicating physiologic relevance....
ABSTRACT Reovirus infections are initiated by the binding of viral attachment protein σ1 to receptors on surface host cells. The is an elongated fiber comprised N-terminal tail that inserts into virion and a C-terminal head extends from surface. prototype reovirus strains type 1 Lang/53 (T1L/53) 3 Dearing/55 (T3D/55) use junctional adhesion molecule A (JAM-A) as receptor. half T3D/55 interacts directly with JAM-A, but determinants receptor-binding specificity have not been identified. In...
SeroNet institutions have developed or implemented 61 diverse COVID-19 serological assays and are collaboratively working to harmonize these using reference materials establish standardized reporting units. This will facilitate clinical interpretation of serology results cross-comparison research data.
Infection of neonatal mice with some reovirus strains produces a disease similar to infantile biliary atresia, but previous attempts correlate infection this have yielded conflicting results. We used isogenic T3SA– and T3SA+, which differ solely in the capacity bind sialic acid as coreceptor, define role encephalitis tract mice. Growth intestine was equivalent for both following peroral inoculation. However, T3SA+ spread more rapidly from distant sites replicated higher titers spleen, liver,...
Reovirus induces apoptosis in cultured cells and vivo. In cell culture models, is contingent upon a mechanism involving reovirus-induced activation of transcription factor NF-κB complexes containing p50 p65/RelA subunits. To explore the vivo role this process, we tested capacity reovirus to induce mice lacking functional nfkb1/p50 gene. The genetic defect had no apparent effect on replication intestine or dissemination secondary sites infection. comparison what was observed wild-type...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seroprevalence studies largely focus on adults, but little is known about spread in children. We determined SARS-CoV-2 children and adolescents from Arkansas over the first year of coronavirus disease 2019 (COVID-19) pandemic.
Abstract Gammaherpesviruses are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For such as Epstein-Barr virus and murine gammaherpesvirus 68, this is accomplished through a viral gene-expression program promotes cellular proliferation differentiation, especially of germinal center B cells. Intrinsic host mechanisms control virus-driven expansion incompletely defined. Using small-animal model pathogenesis, we demonstrate vivo the suppressor p53 activated...
Mammalian reoviruses are nonenveloped viruses with a long, filamentous attachment protein that dictates disease phenotypes following infection of newborn mice and is structural homologue the adenovirus protein. Reoviruses use junctional adhesion molecule 1 (JAM1) as serotype-independent cellular receptor. JAM1 broadly expressed immunoglobulin superfamily forms stable homodimers regulates tight-junction permeability lymphocyte trafficking. We employed series structure-guided binding...
Gammaherpesvirus 68 (gammaHV68, or MHV68) is a naturally occurring rodent pathogen that replicates to high titer in cell culture and amenable vivo experimental evaluation of viral host determinants gammaherpesvirus disease. However, the inability MHV68 transform primary murine B cells culture, absence robust latency system, paucity MHV68-positive tumor lines have limited an understanding molecular mechanisms by which modulates during reactivation. To facilitate more complete regulate...
Murine gammaherpesvirus 68 (MHV68) establishes a lifelong infection in mice and is used as model pathogen to study the role of viral host factors chronic infection. The maintenance MHV68 infection, at least some latency reservoirs, appears be dependent on capacity virus reactivate from vivo. However, signals that lead reactivation vivo are not well characterized. Toll-like receptors (TLRs), by recognizing specific patterns microbial components, play an essential activation innate immunity....
Kaposi's sarcoma-associated herpesvirus (KSHV) causes several human cancers, such as sarcoma (KS) and primary effusion lymphoma (PEL). Current treatment options for KSHV infection virus associated diseases are sometimes ineffective, therefore, more effectively antiviral agents urgently needed. As a herpesvirus, lytic replication is critical pathogenesis oncogenesis. In this study, we have established high-throughput screening assay by using an inducible KSHV+ cell-line, iSLK.219. After...
Abstract Gammaherpesviruses are oncogenic viruses that establish lifelong infections and significant causes of morbidity mortality. Vaccine strategies to limit gammaherpesvirus infection disease in development, but there no FDA-approved vaccines for Epstein-Barr or Kaposi sarcoma herpesvirus. As a new approach vaccination, we developed tested replication-deficient virus (RDV) platform, using murine 68 (MHV68), well-established mouse model pathogenesis studies preclinical therapeutic...
ABSTRACT Apoptosis plays a major role in the cytopathic effect induced by reovirus following infection of cultured cells and newborn mice. Strain-specific differences capacity to induce apoptosis segregate with S1 M2 gene segments, which encode attachment protein σ1 membrane penetration μ1, respectively. Virus strains that bind both junctional adhesion molecule-A (JAM-A) sialic acid are most potent inducers apoptosis. In addition receptor binding, events replication occur during or after...
Gammaherpesviruses establish lifelong, latent infections in host lymphocytes, during which a limited subset of viral gene products facilitates maintenance the episome. Among gamma-2-herpesvirus (rhadinovirus) subfamily, this includes expression conserved ORF73-encoded LANA proteins. We previously demonstrated by loss-of-function mutagenesis that murine gammaherpesvirus 68 (MHV68) ORF73 product, mLANA, is required for establishment latency following intranasal inoculation mice (N. J. Moorman,...
We applied a custom tiled microarray to examine murine gammaherpesvirus 68 (MHV68) polyadenylated transcript expression in time course of de novo infection fibroblast cells and following phorbol ester-mediated reactivation from latently infected B cell line. During infection, all open reading frames (ORFs) were transcribed clustered into four major temporal groups that overlapping yet distinct clusters based on the ester-stimulated course. High-density analysis at 2-h intervals during mapped...
Gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8) establish lifelong latency in their hosts are associated with the development of several types malignancies, including a subset B cell lymphomas. These viruses thought to co-opt process differentiation latently infect fraction circulating memory cells, resulting establishment stable setpoint. However, little is known about how this infected compartment maintained throughout life...