A5048676830- Herpesvirus Infections and Treatments
- Ocular Surface and Contact Lens
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Ocular Infections and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Corneal Surgery and Treatments
- Immune Response and Inflammation
- Corneal surgery and disorders
- Dermatology and Skin Diseases
- Biosimilars and Bioanalytical Methods
- Acne and Rosacea Treatments and Effects
- Ocular Diseases and Behçet’s Syndrome
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- CAR-T cell therapy research
- Toxin Mechanisms and Immunotoxins
- Poxvirus research and outbreaks
- Glaucoma and retinal disorders
- Virus-based gene therapy research
- Toxoplasma gondii Research Studies
- Multiple Myeloma Research and Treatments
- Cell Adhesion Molecules Research
University of Pittsburgh
2011-2020
Eye and Ear Foundation
2009-2018
Kaiser Permanente South San Francisco Medical Center
2014
National Eye Institute
2013
Bioanalytical Systems (United States)
2013
Genentech
2012
Ophthalmology Associates (United States)
1999-2009
Laboratory of Molecular Genetics
2006-2009
Institute of Immunology
2008
Weatherford College
2007
Reactivation of herpes simplex virus type 1 (HSV-1) from neuronal latency is a common and potentially devastating cause disease worldwide. CD8 + T cells can completely inhibit HSV reactivation in mice, with interferon-γ affording portion this protection. We found that cell lytic granules are also required for the maintenance both vivo ex ganglia cultures their directed release to junction neurons latently infected did not induce apoptosis. Here, we describe nonlethal mechanism viral...
BackgroundNeurofilament light chain (NfL), a neuronal cytoskeletal protein that is released upon neuroaxonal injury, associated with multiple sclerosis (MS) relapsing activity and has demonstrated some prognostic ability for future relapse-related disease progression, yet its value in assessing non-relapsing progression remains unclear.MethodsWe examined baseline longitudinal blood NfL levels 1421 persons MS (RMS) 596 primary progressive (PPMS) from the pivotal ocrelizumab trials....
Tiragolumab, an anti-TIGIT antibody with active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716 ) when combined atezolizumab (anti-PD-L1) versus alone
Recurrent herpes simplex virus type 1 (HSV-1) disease usually results from reactivation of latent in sensory neurons and transmission to peripheral sites. Therefore, defining the mechanisms that maintain HSV-1 a state may provide new approaches reducing susceptibility recurrent herpetic disease. After primary corneal infection, CD8+ T cells infiltrate trigeminal ganglia (TGs) mice, are retained latently infected ganglia. Here we demonstrate present TGs at time excision can ex vivo TG...
Herpes simplex virus (HSV) glycoproteins E and I (gE gI) can act as a receptor for the Fc domain of immunoglobulin G (IgG). To examine role HSV IgG in viral pathogenesis, rabbits mice were infected by corneal route with gE- or gI- mutants. Wild-type HSV-1 produced large dendritic lesions epithelium subsequent stromal disease leading to encephalitis, whereas mutant viruses microscopic punctate small no encephalitis. These differences not related ability gE-gI oligomer bind because observed...
Following herpes simplex virus type 1 (HSV-1) infection of the cornea, is transmitted to trigeminal ganglion, where a brief period replication followed by establishment latent in neurons. A possible role immune system regulating and maintaining latency sensory neurons has been suggested. We have investigated phenotype cytokine pattern cells that infiltrate A/J mouse ganglion at various times after HSV-1 corneal infection. HSV antigen expression (indicative viral lytic cycle) increased until...
We recently demonstrated that CD8(+) T cells could block herpes simplex virus type 1 (HSV-1) reactivation from latency in ex vivo trigeminal ganglion (TG) cultures without destroying the infected neurons. Here we establish T-cell prevention of HSV-1 is mediated at least part by gamma interferon (IFN-gamma). demonstrate IFN-gamma was produced dissociated latently TG were present time excision. Depletion or neutralization significantly enhanced rate cultures. When treated with acyclovir for 4...
HSV type 1 (HSV-1) infection of the mouse cornea results in a tissue-destructive inflammatory reaction cornea, but little or no disease skin surrounding eye. Depleting T lymphocytes from mice before HSV-1 corneal prevents inflammation severely exacerbates periocular lesions. Studies described this communication investigated role cell cytokines and induced by infection. Mice received weekly i.p. injections rat mAb specific for IL-2, IL-4, IFN-gamma beginning day (day -1) 6 days after +6) with...
The herpes simplex virus (HSV) infected cell protein (ICP)47 blocks CD8+ T recognition of cells by inhibiting the transporter associated with antigen presentation (TAP). In vivo, HSV-1 replicates in two distinct tissues: epithelial mucosa or epidermis, where enters sensory neurons; and peripheral central nervous system, acute subsequently latent infections occur. Here, we show that an ICP47- mutant is less neurovirulent than wild-type mice, but normally tissues. reduced neurovirulence was...
Herpes simplex virus type 1 (HSV-1) expresses a unique series of RNA molecules, the latency-associated transcripts or LATs, during latent infection neuronal tissues. Previous studies by others have described TATA box-containing latency-active promoter, referred to here as LAP1, located approximately 700 bp upstream 5' end major 2.0-kb LAT. In this report, transient gene expression assays were employed identify second, novel promoter (LAP2) present within region downstream LAP1 and proximal...
Abstract Recurrent HSV-1 ocular disease results from reactivation of latent virus in trigeminal ganglia, often following immunosuppression or exposure to a variety psychological physical stressors. HSV-specific CD8+ T cells can block latency ex vivo ganglia cultures through production IFN-γ. In this study, we establish that either cell depletion restraint stress permit transiently escape vivo. Restraint caused reduction TG-resident and functional compromise those survive. Together, these...
Background: Neurofilament light (NfL) chain is an established cerebrospinal fluid (CSF) biomarker for neuroaxonal injury. The highly sensitive Quanterix Simoa™ platform evaluated NfL measurement in both CSF and blood. There a need to link historical ELISA data that use bovine of Simoa using recombinant human (rhuman) standard. Results/Methodology: NF-light® Advantage Kit was validated qualified serum plasma, rhuman calibrators. Matched CSF, plasma samples from 112 multiple sclerosis patients...
After corneal infection, herpes simplex virus type 1 (HSV-1) invades sensory neurons with cell bodies in the trigeminal ganglion (TG), replicates briefly, and then establishes a latent infection these neurons. HSV-1 replication TG can be detected as early 2 days after reaches peak titers by 3-5 is undetectable 7-10 days. During period of replication, macrophages gammadelta TCR+ T lymphocytes infiltrate TG, TNF-alpha, IFN-gamma, inducible nitric oxide synthase (iNOS) enzyme, IL-12 are...
Increased numbers of T cell receptor (TCR)-γ/δ cells have been observed in animal models influenza and sendai virus infections, as well patients infected with human immunodeficiency herpes simplex type 1 (HSV-1). However, a direct role for TCR-γ/δ protective immunity pathogenic viral infection has not demonstrated. To define the anti–HSV-1 immunity, TCR-α−/− mice treated anti– monoclonal antibodies or × TCR-α/β double-deficient were HSV-1 by footpad ocular routes infection. In both...
Herpes simplex virus type 1 (HSV-1)-specific CD8+ T cells and the cytokine gamma interferon (IFN-gamma) are persistently present in trigeminal ganglia (TG) harboring latent HSV-1. We define "latency" as retention of functional viral genomes sensory neurons without production infectious virions "reactivation" a multistep process leading from latency to virion assembly. can block HSV-1 reactivation ex vivo mouse TG cultures appear be sole source IFN-gamma these cultures. Here we demonstrate...
In a mouse model of herpes simplex virus (HSV) 1 corneal infection, tissue destruction results from CD4+ T cell-mediated chronic inflammation, in which interleukin 2 and interferon (IFN) gamma are requisite inflammatory mediators polymorphonuclear leukocytes (PMN) the predominant infiltrating cells. vivo neutralization IFN-gamma relieved inflammation at least part through specific block PMN extravasation into HSV-1-infected corneas. Intercellular adhesion molecule (ICAM) platelet endothelial...
Abstract Previous studies have revealed that the RE strain of HSV type 1 (HSV-1) induces a tissue-destructive inflammatory response in mouse cornea is mediated by CD4 T lymphocytes, whereas KOS HSV-1 preferentially activates CD8 lymphocytes cornea. Langerhans cells (LC) normally reside only at periphery but can migrate centripetally after infection. We studied relative contribution LC to corneal inflammation induced and strains HSV-1. Ten days infection, central one-third HSV-1-infected...
Abstract HSV type 1 (HSV-1) expresses its genes sequentially as immediate early (α), (β), leaky late (γ1), and true (γ2), where viral DNA synthesis is an absolute prerequisite only for γ2 gene expression. The γ1 protein glycoprotein B (gB) contains a strongly immunodominant CD8+ T cell epitope (gB498–505) that recognized by 50% of both the effector cells in acutely infected trigeminal ganglia (TG) memory latently TG. Of 376 predicted HSV-1 epitopes C57BL/6 mice, 19 (gB498–505 18 subdominant...