A5030230108- Viral Infections and Vectors
- Mosquito-borne diseases and control
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Outbreaks Research
- Vector-Borne Animal Diseases
- COVID-19 Clinical Research Studies
- Fire effects on ecosystems
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 detection and testing
- Animal Virus Infections Studies
- Influenza Virus Research Studies
- Malaria Research and Control
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- interferon and immune responses
- RNA Interference and Gene Delivery
- HIV Research and Treatment
- Long-Term Effects of COVID-19
- Animal Disease Management and Epidemiology
- Virology and Viral Diseases
- COVID-19 diagnosis using AI
- Infection Control and Ventilation
- Inhalation and Respiratory Drug Delivery
- Insect symbiosis and bacterial influences
- Kawasaki Disease and Coronary Complications
National Institutes of Health
2018-2025
National Institute of Allergy and Infectious Diseases
2018-2025
University of Colorado Denver
2013-2024
Office of Extramural Research
2018-2021
Government of the United States of America
2021
State Key Laboratory of Virology
2020
University of Colorado Anschutz Medical Campus
2016
ABSTRACT Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that causes incapacitating disease in humans characterized by intense joint pain can persist for weeks, months, or even years. Although there some evidence of persistent CHIKV infection suffering from chronic rheumatologic symptoms, little known about pathogenesis, and no specific therapies exist acute disease. To investigate mechanisms CHIKV-induced disease, we utilized mouse model defined the duration tissues...
The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is having a deleterious impact on health services and global economy, highlighting urgent need for an effective vaccine. Such vaccine would to rapidly confer protection after one or two doses be manufactured using components suitable scale up. Here, we developed
The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would substantial benefit controlling pandemic. Herein, we show MK-4482, an nucleoside analog, inhibits replication Syrian hamster model. inhibitory effect MK-4482 on is observed animals when drug either beginning 12 h before or infection a These data support potential utility to control humans as well...
<ns4:p>Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed and the cause of disease in Africa, Southern Eastern Europe, Middle East, India Asia. Recent emergence CCHFV into Spain indicates that geographic range this expanding presence its tick vector several countries without reported suggest will continue to spread. Research was historically limited by lack suitable animal models tools study viral pathogenesis. However, past few years toolset for studying has expanded with...
BackgroundCrimean-Congo hemorrhagic fever virus is the cause of a severe with cases reported throughout wide-geographic region. Spread by bite infected ticks, contact livestock or in health care setting, disease begins as non-specific febrile illness that can rapidly progress to manifestations. Currently, there are no approved vaccines and antivirals such ribavirin have unclear efficacy. Thus treatment mostly limited supportive care.MethodsIn this report we evaluated an alphavirus-based...
Abstract Climate change and population densities accelerated transmission of highly pathogenic viruses to humans, including the Crimean–Congo haemorrhagic fever virus (CCHFV). Here we report that Low Density Lipoprotein Receptor (LDLR) is a critical receptor for CCHFV cell entry, playing vital role in infection culture blood vessel organoids. The interaction between LDLR specific, with other members protein family failing bind or neutralize virus. Biosensor experiments demonstrate...
Abstract Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne febrile illness with wide geographic distribution. In recent years the range of virus (CCHFV) and its tick vector have increased, placing an increasing number people at risk CCHFV infection. Currently, there are no widely available vaccines, although World Health Organization recommends ribavirin for treatment, efficacy unclear. Here we evaluate promising replicating RNA vaccine in rhesus macaque ( Macaca mulatta) model CCHF....
Abstract The ongoing circulation of influenza A H5N1 in the United States has raised concerns a pandemic caused by highly pathogenic avian influenza. Although stockpiled and is prepared to produce millions vaccine doses address an pandemic, currently circulating viruses contain multiple mutations within immunodominant head domain hemagglutinin (HA) compared antigens used vaccines. It unclear if these vaccines will need be updated match contemporary strains. Here we show that replicating RNA...
Chikungunya virus (CHIKV) and related alphaviruses cause epidemics of acute chronic musculoskeletal disease. To investigate the mechanisms underlying failure immune clearance CHIKV, we studied mice infected with an attenuated CHIKV strain (181/25) pathogenic parental (AF15561), which differ by five amino acids. Whereas AF15561 infection wild-type results in viral persistence joint tissues, 181/25 is cleared. In contrast, μMT lacking mature B cells suggesting that virus-specific antibody...
ABSTRACT Chikungunya virus (CHIKV) is a reemerging mosquito-transmitted alphavirus that causes epidemics of debilitating polyarthritis in humans. A prior study identified two anti-CHIKV monoclonal antibodies ([MAbs] CHK-152 and CHK-166) against the E2 E1 structural proteins, which had therapeutic efficacy immunocompetent immunocompromised mice. Combination MAb therapy was required as administration single resulted rapid selection neutralization escape variants treatment failure Here, we...
Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. CCHF caused by infection the virus (CCHFV) and case fatality rates can be as high 30%. Despite causing disease in humans, our understanding of host viral determinants CCHFV pathogenesis are limited. A major limitation investigation has been lack suitable small animal models. Wild-type mice resistant to clinical isolates consequently, must deficient type I interferon responses...
Despite mass public health efforts, the SARS-CoV2 pandemic continues as of late 2021 with resurgent case numbers in many parts world. The emergence variants concern (VoCs) and evidence that existing vaccines were designed to protect from original strains SARS-CoV-2 may have reduced potency for protection infection against these VoC is driving continued development second-generation can multiple VoC. In this report, we evaluated an alphavirus-based replicating RNA vaccine expressing Spike...
The recent emergence and rapid response to severe acute respiratory syndrome coronavirus 2 was enabled by prototype pathogen vaccine platform approaches, driven the preemptive application of RNA technology related Middle East coronavirus. Recently, National Institutes Allergy Infectious Diseases identified nine virus families concern, eight enveloped one nonenveloped family, for which generation is a priority. Although vaccines have been described variety viruses, roadmap their use against...
Infections with New World hantaviruses are associated high case fatality rates, and no specific vaccine or treatment options exist. Furthermore, the biology of hantaviral GnGc complex, its antigenicity, fusion machinery poorly understood. Protective monoclonal antibodies against have potential to be developed into therapeutics disease also great tools elucidate glycoprotein complex.
We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the hydroxychloroquine (HCQ), interest COVID-19 management, in two animal models. When used prophylaxis or treatment neither standard malaria dose (6.5 mg/kg) nor high (50 HCQ had any beneficial effect on disease SARS-CoV-2 kinetics (replication/shedding) Syrian...
We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human COVID-19 clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies to help guide decisions. Here we assessed the hydroxychloroquine (HCQ), interest management, in 2 animal disease models. The standard malaria HCQ prophylaxis (6.5 mg/kg given weekly) and treatment daily) did not significantly benefit outcome, nor it reduce SARS-CoV-2...
Severe coronavirus disease 2019 (COVID-19) has been associated with T cell lymphopenia, but no causal effect of deficiency on severity established. To investigate the specific role cells in recovery from severe acute respiratory syndrome 2 (SARS-CoV-2) infections, we studied rhesus macaques that were depleted either CD4+, CD8+, or both subsets prior to infection. Peak virus loads similar all groups, resolution cell-depleted animals was slightly delayed compared controls. The groups developed...