A5010789104- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Vectors
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Viral Infections and Outbreaks Research
- Virology and Viral Diseases
- Animal Virus Infections Studies
- Respiratory viral infections research
- SARS-CoV-2 detection and testing
- Vector-borne infectious diseases
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
- COVID-19 epidemiological studies
- Long-Term Effects of COVID-19
- Autophagy in Disease and Therapy
- Disaster Response and Management
- Animal Disease Management and Epidemiology
- HIV Research and Treatment
- Vector-Borne Animal Diseases
- Yersinia bacterium, plague, ectoparasites research
- Bacillus and Francisella bacterial research
- vaccines and immunoinformatics approaches
- Zoonotic diseases and public health
- Burkholderia infections and melioidosis
- Immune responses and vaccinations
National Institute of Allergy and Infectious Diseases
2015-2024
National Institutes of Health
2012-2024
Columbia University
2017
Rocky Mountain College
2010
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure urgently needed to control pandemic4. Here we show that adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes spike protein of SARS-CoV-2, immunogenic mice elicites a robust humoral cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated...
An outbreak of coronavirus disease 2019 (COVID-19), which is caused by a novel (named SARS-CoV-2) and has case fatality rate approximately 2%, started in Wuhan (China) December 20191,2. Following an unprecedented global spread3, the World Health Organization declared COVID-19 pandemic on 11 March 2020. Although data humans are emerging at steady pace, some aspects pathogenesis SARS-CoV-2 can be studied detail only animal models, repeated sampling tissue collection possible. Here we show that...
SARS-CoV-2 emerged in late 2019 and resulted the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate asymptomatic to moderate disease spectrum. Now, there is a direct need for additional small study pathogenesis of severe fast-tracked medical countermeasure development. Here, we show transgenic mice expressing human receptor (angiotensin-converting enzyme 2 [hACE2]) under cytokeratin 18 promoter (K18) are susceptible infection dose-dependent lethal...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 2019 1,2 and is responsible for the COVID-19 pandemic 3 . Vaccines are an essential countermeasure urgently needed to control 4 Here, we show that adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding spike protein of SARS-CoV-2, immunogenic mice, eliciting a robust humoral cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass cytokine expression profiling. A single...
Abstract The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential Betacoronaviruses . Investigations into origin MERS-CoV have focused on two reservoirs: bats and camels. Here, we investigated role as a reservoir for MERS-CoV. In vitro , spike glycoprotein interacted with Jamaican fruit bat ( Artibeus jamaicensis ) dipeptidyl peptidase 4 (DPP4) receptor replicated efficiently in cells, suggesting there is no restriction at or cellular level...
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...
An outbreak of a novel coronavirus, now named SARS-CoV-2, causing respiratory disease and ~2% case fatality rate started in Wuhan, China December 2019. Following unprecedented rapid global spread, the World Health Organization declared COVID-19 pandemic on March 11, 2020. Although data humans are emerging at steady pace, certain aspects pathogenesis SARS-CoV-2 can only be studied detail animal models, where repeated sampling tissue collection is possible. Here, we show that causes infected...
Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine currently available. While the nonhuman primate (NHP) model used final evaluation of experimental vaccines and therapeutic efficacy, rodent models have been widely in ebolavirus research because their convenience. However, validity has questioned given low predictive value efficacy testing therapeutics, result inconsistent manifestation coagulopathy seen EHF. Here, we describe lethal Syrian...
Abstract Encephalitis is a hallmark of Nipah virus (NiV) infection in humans. The exact route entry NiV into the central nervous system (CNS) unknown. Here, we performed spatio-temporal analysis CNS hamsters. initially predominantly targeted olfactory epithelium nasal turbinates. From there, infected neurons were visible extending through cribriform plate bulb, providing direct evidence rapid entry. Subsequently, disseminated to tubercle and throughout ventral cortex. Transmission electron...
ABSTRACT The first influenza pandemic of the new millennium was caused by a newly emerged swine-origin virus (SOIV) (H1N1). This is characterized previously unknown constellation gene segments derived from North American and Eurasian swine lineages absence common markers predictive human adaptation. Overall, infections appeared to be mild, but an alarming number young individuals presented with symptoms atypical for seasonal influenza. SOIV also showed sustained human-to-human...
Significance Hantavirus pulmonary syndrome (HPS) is a rare but often fatal disease caused by infection with New World hantaviruses. A limitation to understanding the pathogenesis of HPS and developing medical countermeasures against this lack experimental models. In study we describe characterization novel nonhuman primate model HPS. After deer mouse-only–passaged Sin Nombre virus, macaques developed severe respiratory indicative Viremia hematological abnormalities were earliest markers...
A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-03099-2
The recent emergence of the SARS-CoV-2 Omicron variant concern (VOC), which contains a heavily mutated spike protein capable escaping preexisting immunity, identifies continued need for interventional measures. Molnupiravir (MK-4482), an orally administered nucleoside analog, has demonstrated efficacy against earlier lineages and was recently approved infections in high-risk adults. Here, we assessed MK-4482 Alpha, Beta, Delta VOCs hamster COVID-19 model. replication associated lung disease...
Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19) and is influenced by host genetics. To understand mechanisms inflammation, animal models that reflect genetic diversity clinical outcomes observed humans are needed. We report a mouse panel comprising the genetically diverse Collaborative Cross (CC) founder strains crossed human ACE2 transgenic mice (K18-hACE2) confers susceptibility...
Hantavirus pulmonary syndrome (HPS), also referred to as hantavirus cardiopulmonary (HCPS), is a rare but frequently fatal disease caused by New World hantaviruses. In humans HPS associated with severe edema and cardiogenic shock; however, the pathogenesis of this remains unclear largely due lack suitable animal models for study progression. we monitored clinical, virological, pathophysiological parameters host immunological responses decipher pathological factors events in lethal Syrian...
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...
Dysregulated inflammation dominated by chemokine expression is a key feature of disease following infection with the globally important human pathogens Zika virus (ZIKV) and dengue virus, but mechanistic understanding how pro-inflammatory responses are initiated lacking. Mitophagy quality-control mechanism that regulates innate immune signaling cytokine production through selective degradation damaged mitochondria. Here, we demonstrate ZIKV nonstructural protein 5 (NS5) antagonizes mitophagy...
In nature prion diseases are usually transmitted by extracerebral infection, but clinical disease results only after invasion of the central nervous system (CNS). Prion protein (PrP), a host-encoded glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein, is necessary for infection and disease. Here, we investigated role anchoring PrP on neuroinvasion studying various inoculation routes in mice expressing either anchored or anchorless PrP. control with PrP, intracerebral sciatic...
ABSTRACT A delayed inflammatory response is a prominent feature of infection with Yersinia pestis , the agent bubonic and pneumonic plague. Using rat model plague, we examined lymph node histopathology, transcriptome, extracellular cytokine levels to broadly characterize kinetics extent host Y. how it influenced by virulence plasmid (pYV). Remarkably, dissemination multiplication wild-type during stage disease did not induce any detectable gene expression or cells in developing bubo. Only...
Abstract Although Zika virus (ZIKV) is primarily transmitted to humans by the Aedes aegypti mosquito, human-to-human transmission has also been observed from males-to-females as well mother-to-offspring. In current study, we studied both sexual (STx) and vertical (VTx) of ZIKV using anti-IFNAR1-treatment Rag1 −/− (AIR) mice. These mice have suppressed type I IFN responses lack adaptive immune responses, leading a prolonged infection prior clinical disease. STx infected AIR males naive Ifnar1...
Ebola virus (EBOV), variant Makona, was the causative agent of 2013-2016 West African epidemic responsible for almost 30,000 human infections and over 11,000 fatalities. During epidemic, development several experimental vaccines accelerated through clinical trials. One them, vesicular stomatitis (VSV)-based vaccine VSV-EBOV, showed promising efficacy in a phase 3 trial Guinea is currently used ongoing EBOV outbreak northeastern part Democratic Republic Congo (DRC). This expresses EBOV-Kikwit...
is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by
Human cases of SARS-CoV-2 reinfection have been documented throughout the pandemic, but are likely under-reported. In current study, we use Syrian hamster model to assess with homologous WA1 and heterologous B.1.1.7 (Alpha) B.1.351 (Beta) variants over time. Upon primary infection WA1, hamsters rapidly develop a strong long-lasting humoral immune response. After variants, this response protects from clinical disease, virus replication in lower respiratory tract, acute lung pathology....