A5077474793- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Malaria Research and Control
- Viral Infections and Outbreaks Research
- Viral-associated cancers and disorders
- Reproductive tract infections research
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Microfluidic and Bio-sensing Technologies
- Phagocytosis and Immune Regulation
- Advanced biosensing and bioanalysis techniques
- Immunotherapy and Immune Responses
- Photonic and Optical Devices
- Polyomavirus and related diseases
- Immunodeficiency and Autoimmune Disorders
- Studies on Chitinases and Chitosanases
- Immune Response and Inflammation
- COVID-19 Clinical Research Studies
- Magnetic Field Sensors Techniques
- Trypanosoma species research and implications
- Chronic Myeloid Leukemia Treatments
- Toxoplasma gondii Research Studies
University of California, Berkeley
2015-2024
Berkeley College
2011
Ministerio de Salud Pública
2009
Stanford University
1997-2002
American Society of Transplantation
1998
National Institutes of Health
1998
San Francisco Foundation
1996-1997
Stanford Medicine
1997
Dokkyo University
1992
Medical College of Wisconsin
1987
The four dengue virus serotypes (DENV1 to DENV4) are mosquito-borne flaviviruses that cause up ~100 million cases of annually worldwide. Severe disease is thought result from immunopathogenic processes involving serotype cross-reactive antibodies and T cells together induce vasoactive cytokines, causing vascular leakage leads shock. However, no viral proteins have been directly implicated in triggering endothelial permeability, which results leakage. DENV nonstructural protein 1 (NS1)...
Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype. Serotype cross-reactive antibodies facilitate myeloid cells vitro by promoting entry via Fcgamma receptors (FcgammaR), a process known as antibody-dependent enhancement (ADE). However, despite decades investigation, no vivo model for antibody has been described. Analogous human infants who receive anti-DV transplacental transfer and develop...
Lack of an appropriate animal model for dengue virus (DEN), which causes fever and hemorrhagic fever/dengue shock syndrome (DHF/DSS), has impeded characterization the mechanisms underlying disease pathogenesis. The cardinal feature DHF/DSS, severe form DEN infection, is increased vascular permeability. To develop a murine that more relevant to novel strain, D2S10, was generated by alternately passaging non-mouse-adapted strain between mosquito cells mice, thereby mimicking natural...
Flaviviruses cause systemic or neurotropic-encephalitic pathology in humans. The flavivirus nonstructural protein 1 (NS1) is a secreted glycoprotein involved viral replication, immune evasion, and vascular leakage during dengue virus infection. However, the contribution of NS1 from related flaviviruses to pathogenesis remains unknown. Here, we demonstrate that dengue, Zika, West Nile, Japanese encephalitis, yellow fever viruses selectively binds alters permeability human endothelial cells...
Two antibodies against flaviviruses Flaviviruses are a group of RNA viruses that include the human pathogens dengue virus, Zika and West Nile virus. The envelope protein (E) on virus surface has been target vaccine development, but problems have arisen with E, leading to enhanced infection. Now, Modhiran et al. Biering describe two different bind flavivirus NS1 prevent it from disrupting epithelial cells, which is associated severe disease. Both cross-react multiple proteins. reduce viremia...
Dengue virus (DEN) causes dengue fever and hemorrhagic fever/dengue shock syndrome, which are major public health problems worldwide. The immune factors that control DEN infection or contribute to severe disease neither well understood nor easy examine in humans. In this study, we used wild-type congenic mice lacking various components of the system study mechanisms response infection. Our results demonstrate alpha/beta interferon (IFN-alpha/beta) IFN-gamma receptors have critical,...
Previous attempts to define dengue virus (DENV) tropism in human autopsy tissues have detected DENV antigens that are abundant circulation during severe dengue, and thus may be present uninfected cells. To better tropism, we performed immunostaining for the DENV2 nonstructural protein 3 (NS3) humans a mouse model of infection. In mice, NS3 was phagocytes spleen lymph node, hepatocytes liver, myeloid cells bone marrow. tissues, node spleen, alveolar macrophages lung, perivascular brain. This...
Dengue virus (DENV) is the most prevalent, medically important mosquito-borne virus. Disease ranges from uncomplicated dengue to life-threatening disease, characterized by endothelial dysfunction and vascular leakage. Previously, we demonstrated that DENV nonstructural protein 1 (NS1) induces hyperpermeability in a systemic mouse model human pulmonary cells, where NS1 disrupts glycocalyx-like layer. also triggers release of inflammatory cytokines PBMCs via TLR4. Here, examined relative...
Dengue fever is a mosquitoborne viral illness caused by 4 dengue viruses (DENV-1-4). The cellular tropism of DENV has not been definitively determined, despite its importance for understanding pathogenesis and identifying therapeutic targets. To define in small animal model, 129/Pas mice lacking interferon-alpha/beta and/or-gamma receptors were infected with via subcutaneous route. During the first week after infection, virus was present lymph nodes, spleen, bone marrow, circulating white...
Abstract Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well in distal organs. While it appreciated that an exaggerated inflammatory response dysfunction, triggers of vascular leak are unclear. Here, we report cell-intrinsic interactions between Spike (S) glycoprotein SARS-CoV-2 epithelial/endothelial cells sufficient to induce vitro vivo, independently viral replication ACE2 receptor. We identify S-triggered transcriptional extracellular...
Abstract Immunocompromised individuals have an increased incidence of EBV-associated B cell lymphomas. The growth factors responsible for the unrestrained proliferation these lymphomas not yet been determined. In this study, spontaneous lymphoblastoid lines (SLCL) were derived without addition or virus from four patients with lymphoproliferative disorder. These EBV transformed in vivo, and infection was verified through amplification viral gp220 gene. SLCL activated phenotype (CD19+, CD21+,...
Abstract Dengue virus (DEN), a flavivirus, causes dengue fever and hemorrhagic fever/dengue shock syndrome, the most common mosquito-borne viral illnesses in humans worldwide. In this study, using STAT1−/− mice bearing two different mutant stat1 alleles 129/Sv/Ev background, we demonstrate that IFNR-dependent control of primary DEN infection involves both STAT1-dependent STAT1-independent mechanisms. The STAT1 pathway is necessary for clearing initial load, whereas controls later burden...
Abstract The four dengue virus (DENV) serotypes cause fever and hemorrhagic fever/dengue shock syndrome. Although severe disease has been associated with heterotypic secondary DENV infection, most infections are asymptomatic or result in classic DF. role of cross-reactive immunity mediating cross-protection against infection is not well understood. IFN-α/β IFN-γ receptor-deficient (AG129) mice reproduces key features human disease. We previously demonstrated a for pre-existing Abs,...
It has long been thought that iminosugar antiviral activity is a function of inhibition endoplasmic reticulum-resident α-glucosidases, and on this basis, many iminosugars have investigated as therapeutic agents for treatment infection by diverse spectrum viruses, including dengue virus (DENV). However, are glycomimetics possessing nitrogen atom in place the endocyclic oxygen atom, ubiquity glycans host metabolism suggests multiple pathways can be targeted via treatment. Successful patients...
The antiviral activity of UV-4 was previously demonstrated against dengue virus serotype 2 (DENV2) in multiple mouse models. Herein, step-wise minimal effective dose and therapeutic window efficacy studies UV-4B (UV-4 hydrochloride salt) were conducted an antibody-dependent enhancement (ADE) model severe DENV2 infection AG129 mice lacking types I II interferon receptors. Significant survival benefit with 10-20 mg/kg administered thrice daily (TID) for seven days initiation treatment up to 48...
A small animal model for studying dengue disease is of critical importance to furthering many areas research, including host immunity, pathogenesis, and drug vaccine development. Recent characterization the AG129 mouse has demonstrated it be one only models at this time that permits infection by all four serotypes virus (DENV), supports replication in relevant cell tissue types comparable human infection, allows antibody-mediated protection enhancement DENV infection. Thus, enables testing...
Abstract Dengue is a global public health problem and caused by four dengue virus (DENV) serotypes (DENV1-4). A major challenge in vaccine development that cross-reactive anti-DENV Abs can be protective or potentially increase disease via Ab-dependent enhancement. DENV nonstructural protein 1 (NS1) has long been considered candidate as it avoids In this study, we evaluated survival to lethal vascular leak model mice immunized with NS1 combined aluminum magnesium hydroxide, monophosphoryl...
The flavivirus nonstructural protein 1 (NS1) is secreted from infected cells and contributes to endothelial barrier dysfunction vascular leak in a tissue-dependent manner. This phenomenon occurs part via disruption of the glycocalyx layer (EGL) lining endothelium. Additionally, we others have shown that soluble DENV NS1 induces disassembly intercellular junctions (IJCs), group cellular proteins critical for maintaining homeostasis regulating permeability; however, specific mechanisms by...
Abstract Intracellular bacterial pathogens have evolved to either grow in the nutrient-rich cytoplasm or remain sequestered within a vacuole. One potentially important selective advantage for growth vacuole may be evasion of cell-mediated detection and cytolysis. To address this question we used endosomally confined bacterium Chlamydia trachomatis, which naturally infects epithelial cells, examine CTL-mediated lysis nonphagocytic cells. infected target cells was detected, although increased...
Dengue is a mosquito-borne disease of global public health significance that caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from relatively mild self-limiting illness severe life-threatening disease. Infection with one serotype results life-long homotypic immunity only short term heterotypic protection. There no licensed vaccines or antivirals for dengue due part difficulty...