A5063730724- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Malaria Research and Control
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Insect symbiosis and bacterial influences
- Virology and Viral Diseases
- COVID-19 epidemiological studies
- Immune Cell Function and Interaction
- interferon and immune responses
- SARS-CoV-2 detection and testing
- Viral Infections and Outbreaks Research
- Cytomegalovirus and herpesvirus research
- Animal Disease Management and Epidemiology
- Vector-borne infectious diseases
- Influenza Virus Research Studies
- Long-Term Effects of COVID-19
- T-cell and B-cell Immunology
- COVID-19 Impact on Reproduction
- Herpesvirus Infections and Treatments
- Animal Virus Infections Studies
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- Polyomavirus and related diseases
- HIV Research and Treatment
University of Kentucky
2023-2025
Saint Louis University
2017-2024
George Washington University
2023
Saint Louis University
2019-2022
UCLouvain Saint-Louis Brussels
2019-2022
Washington University in St. Louis
2009-2015
Oregon National Primate Research Center
2007-2012
Oregon Health & Science University
2004-2012
Vaccine and Gene Therapy Institute
2007-2009
Children's Cancer Therapy Development Institute
2004-2009
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes global epidemics of debilitating polyarthritis in humans. As there pressing need for the development therapeutic agents, we screened 230 new mouse anti-CHIKV monoclonal antibodies (MAbs) their ability to inhibit infection all three CHIKV genotypes. Four 36 neutralizing MAbs (CHK-102, CHK-152, CHK-166, and CHK-263) provided complete protection against lethality as prophylaxis highly susceptible immunocompromised mice...
Cytokine storm is suggested as one of the major pathological characteristics SARS-CoV-2 infection, although mechanism for initiation a hyper-inflammatory response, and multi-organ damage from viral infection poorly understood. In this virus-cell interaction study, we observed that or spike protein expression alone inhibited angiotensin converting enzyme-2 (ACE2) receptor expression. The promoted an II type 1 (AT1) mediated signaling cascade, induced transcriptional regulatory molecules NF-κB...
Abstract Zika virus (ZIKV) is a re-emerging that has recently spread into dengue (DENV) endemic regions and cross-reactive antibodies (Abs) could potentially affect ZIKV pathogenesis. Using DENV-immune serum, it been shown in vitro antibody-dependent enhancement (ADE) of infection can occur. Here we study the effects pre-existing DENV immunity on vivo . We infect two cohorts rhesus macaques with ZIKV; one cohort exposed to 2.8 years earlier second control naïve flaviviral infection. Our...
The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent spread of severe acute respiratory syndrome 2 (SARS-CoV-2). Intranasal is an attractive strategy COVID-19 as nasal mucosa represents first-line barrier SARS-CoV-2 entry. current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity. Here, we tested a single intranasal dose our candidate adenovirus type 5-vectored vaccine...
ABSTRACT Dengue virus (DENV) is the most prevalent insect-transmitted viral disease in humans globally, and currently no specific therapy or vaccine available. Protection against DENV other related flaviviruses associated with development of antibodies envelope (E) protein. Although prior studies have characterized neutralizing activity monoclonal (MAbs) type 2 (DENV-2), none compared simultaneously inhibitory a genetically diverse range strains vitro , protective capacity animals,...
Antibody protection against flaviviruses is associated with the development of neutralizing antibodies viral envelope (E) protein. Prior studies West Nile virus (WNV) identified therapeutic mouse and human monoclonal (MAbs) that recognized epitopes on domain III (DIII) E To identify an analogous panel DENV type-1 (DENV-1), we immunized mice a genotype 2 strain DENV-1 generated 79 new MAbs, 16 which strongly inhibited infection by homologous localized to DIII. Surprisingly, only two...
Abstract CD4 T cells have been shown to be necessary for the prevention of encephalitis during West Nile virus (WNV) infection. However, mechanisms used by Ag-specific protect mice from WNV remain incompletely understood. Contrary belief that are protective because they merely maintain CD8 cell response and improve Ab production, in this study we provide evidence direct antiviral activity functions host encephalitis. In adoptive transfers, naive protected a significant number lethally...
West Nile virus (WNV) infection causes a life-threatening meningoencephalitis that becomes increasingly more prevalent over the age of 50 and is 40–50× in people 70, compared with adults under 40. In mouse model age-related vulnerability to WNV, we demonstrate death correlates increased viral titers brain this loss control was result defects CD4 CD8 T cell response against WNV. Specific responses dominant WNV epitopes were detected at level cytokine lytic granule production, each which are...
Dengue viruses (DENV) comprise a family of related positive-strand RNA that infect up to 100 million people annually. Currently, there is no approved vaccine or therapy prevent infection diminish disease severity. Protection against DENV associated with the development neutralizing antibodies recognize viral envelope (E) protein. Here, goal identifying monoclonal (MAbs) can function as postexposure therapy, we generated panel 82 new MAbs DENV-3, including 24 highly MAbs. Using yeast surface...
Type I interferon (IFN) signaling coordinates an early antiviral program in infected and uninfected cells by inducing IFN-stimulated genes (ISGs) that modulate viral entry, replication, assembly. However, the specific functions vivo of most ISGs remain unknown. Here, we examined contribution ISG viperin to control West Nile virus (WNV) genetically deficient mice. While modest increases levels WNV replication were observed for primary viperin(-/-) macrophages dendritic cells, no appreciable...
Prominent immune alterations associated with aging include the loss of naïve T-cell numbers, diversity and function. While genetic contributors mechanistic details in process have been addressed multiple studies, role environmental agents remains incompletely understood. From standpoint infectious agents, latent cytomegalovirus (CMV) infection has an risk profile elderly humans, yet cause-effect relationship this association unclear. Here we present direct experimental evidence that mouse...
Abstract West Nile virus (WNV) is a member of the Flaviviridae family enveloped, single‐stranded, positive‐sense RNA viruses. WNV, an emerging viral pathogen, transmitted by mosquitoes to birds and mammals responsible for increasing incidence human disease in North America Europe. Due its ease use laboratory availability robust mouse models disease, WNV provides excellent experimental system studying molecular virology pathogenesis infection flaviviruses. Here, we describe common techniques...
Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection the severe debilitating poly-arthralgia may persist for several months after viral clearance. Since its re-emergence in 2004, has spread from Indian Ocean region to new locations including metropolitan Europe, Japan, even United States. risk importing areas world increasing due high levels viremia infected...
Abstract Vaccination with vaccinia virus (VACV) elicits heterotypic immunity to smallpox, monkeypox, and mousepox, the mechanistic basis for which is poorly understood. It generally assumed that arises from presentation of a wide array VACV-derived, CD8 + T cell epitopes share homology other poxviruses. Herein this assumption was tested using large panel VACV-derived peptides presented by HLA-B*07:02 (B7.2) molecules in mousepox/ectromelia (ECTV)-infection, B7.2 transgenic mouse model. Most...
Zika virus (ZIKV) has gained worldwide attention since it emerged, and a global effort is underway to understand the correlates of protection develop diagnostics identify rates infection. As new therapeutics vaccine approaches are evaluated in clinical trials, additional focused on identifying adaptive immune against ZIKV disease. To aid this endeavor we have begun dissect role CD4+T cells neuroinvasive We identified an important for protection, demonstrating that absence mice more severe...
With 400 million worldwide infections each year, dengue is the most common vector-borne viral disease. Forty percent of world's population at risk, with experiencing consistent geographic spread over years.
This study investigates the dynamics of oleate hydratase (OhyA), a bacterial flavoenzyme from Staphylococcus aureus, and its interactions with lipid membranes, focusing on factors influencing membrane binding oligomerization. OhyA catalyzes hydration unsaturated fatty acids, playing key role in pathogenesis by neutralizing host antimicrobial acids. binds bilayer to access membrane-embedded substrates for catalysis, structural studies have revealed that forms oligomers surfaces, stabilized...
West Nile virus (WNV) is a small, positive-strand RNA belonging to the Flaviviridae genus, which causes lethal encephalitis in subset of infected birds and mammals. In humans, WNV exhibits pronounced age-related morbidity mortality, but basis this effect unclear, molecular cellular parameters host-WNV infection are just beginning be elucidated. Indeed, numerous mechanisms were implicated protection vivo against (IFN-I IFN-gamma, antibody, C', CD8 CD4 T cells), individual importance each one...
A genetic absence of the common IFN- α/β signaling receptor (IFNAR) in mice is associated with enhanced viral replication and altered adaptive immune responses. However, analysis IFNAR-/- limited for studying functions type I IFN at discrete stages infection. To define temporal context infection by West Nile virus (WNV), we treated MAR1-5A3, a neutralizing, non cell-depleting anti-IFNAR antibody. Inhibition or before day 2 after was markedly burden, whereas treatment 4 had substantially less...
Interferon regulatory factor (IRF)-1 is an immunomodulatory transcription that functions downstream of pathogen recognition receptor signaling and has been implicated as a regulator type I interferon (IFN)-αβ expression the immune response to virus infections. However, this role for IRF-1 remains controversial because altered IFN responses have not systemically observed in IRF-1(-/-) mice. To evaluate relationship regulation, we assessed West Nile (WNV) infectivity host cells mice were...
ABSTRACT Although prior studies have characterized the neutralizing activities of monoclonal antibodies (MAbs) against dengue virus (DENV) serotypes 1, 2, and 3 (DENV-1, DENV-2, DENV-3), few reports assessed activity MAbs DENV-4. Here, we evaluated inhibitory 81 new mouse anti-DENV-4 MAbs. We observed strain- genotype-dependent differences in neutralization DENV-4 by mapping to epitopes on domain II (DII) DIII envelope (E) protein. Several inefficiently inhibited at least one strain and/or...
Members of the flavivirus genus share a high level sequence similarity and often circulate in same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. In this study, we tested pools epitopes derived from dengue (DENV), Zika (ZIKV), Japanese encephalitis (JEV), West Nile (WNV), yellow fever (YFV) viruses intracellular cytokine staining (ICS) using peripheral blood mononuclear (PBMCs)...