A5008605683- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Viral Infections and Outbreaks Research
- Poxvirus research and outbreaks
- Herpesvirus Infections and Treatments
- Vector-Borne Animal Diseases
- Bacillus and Francisella bacterial research
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Respiratory viral infections research
- Fire effects on ecosystems
- Virology and Viral Diseases
- Insect symbiosis and bacterial influences
- Fungal Infections and Studies
- Viral-associated cancers and disorders
- Animal Disease Management and Epidemiology
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Infectious Encephalopathies and Encephalitis
- Homelessness and Social Issues
- SARS-CoV-2 detection and testing
- Vibrio bacteria research studies
United States Army Medical Research Institute of Infectious Diseases
2015-2024
University of Minnesota
2002-2011
United States Department of the Army
2009
University of Minnesota Medical Center
2002
Rutgers, The State University of New Jersey
1999
The emergence of SARS-CoV-2 has created an international health crisis, and small animal models mirroring human disease are essential for medical countermeasure (MCM) development. Mice refractory to infection owing low-affinity binding the murine angiotensin-converting enzyme 2 (ACE2) protein. Here, we evaluated pathogenesis in male female mice expressing ACE2 gene under control keratin 18 promoter (K18). In contrast nontransgenic mice, intranasal exposure K18-hACE2 animals different doses...
Animal models are needed to better understand the pathogenic mechanisms of Zika virus (ZIKV) and evaluate candidate medical countermeasures. Adult mice infected with ZIKV develop a transient viremia, but do not demonstrate signs morbidity or mortality. Mice deficient in type I combination II interferon (IFN) responses highly susceptible infection; however, absence competent immune system limits their usefulness for studying Here we employ murine model using wild-type C57BL/6 treated an...
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne capable of causing severe disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed DNA vaccine expressing the M-segment glycoprotein precursor gene CCHFV and assessed its immunogenicity protective efficacy two lethal mouse models disease: type I interferon receptor knockout (IFNAR-/-) mice; novel transiently immune suppressed (IS) model. Vaccination mice by muscle...
An antibody targeting the CCHFV GP38 molecule protects adult mice against lethal infection in a severe disease model.
Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a WHO priority pathogen. Antibody-based medical countermeasures offer an important strategy to mitigate severe disease caused by CCHFV. Most efforts have focused on targeting the viral glycoproteins. However, glycoproteins are poorly conserved among strains. The CCHFV nucleocapsid protein (NP) highly between Here, we investigate protective efficacy of monoclonal antibody NP. We find that anti-NP (mAb-9D5) protected female mice against...
Zika virus (ZIKV) is a mosquito-borne member of the genus Flavivirus that has emerged since 2007 to cause outbreaks in Africa, Asia, Oceania, and most recently, Americas. Here, we used an isolate history as well genetic phylogenetic analyses characterize three low-passage isolates representing African (ArD 41525) Asian (CPC-0740, SV0127-14) lineages investigate potential phenotypic differences vitro vivo. The displayed large plaque phenotype (∼3-4 mm) on Vero HEK-293 cells, whereas either...
Animal models recapitulating human COVID-19 disease, especially severe are urgently needed to understand pathogenesis and evaluate candidate vaccines therapeutics. Here, we develop novel severe-disease animal for involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or
Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe hepatic injury in humans. However, the mechanism(s) causing this damage is poorly characterized. CCHFV produces an acute disease, including liver damage, mice lacking type I interferon (IFN-I) signaling due to either STAT-1 gene deletion or disruption of IFN-I receptor 1 gene. Here, we explored CCHFV-induced pathogenesis using antibody disrupt signaling. When blockade was induced within 24 h postexposure CCHFV, developed disease...
Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne that causes severe disease in humans. Currently, no licensed CCHF vaccines exist, and the protective epitopes remain unclear. Previously, we tested DNA vaccine expressing M-segment glycoprotein precursor gene of laboratory CCHFV strain IbAr 10200 (CCHFV-M ). CCHFV-M provided >60% protection against homologous CCHFV-IbAr challenge mice. Here, report increasing dose provides complete from mice, significant (80%) with...
The eradication of smallpox and subsequent cessation vaccination have left a majority the population susceptible to variola virus or other emerging poxviruses. This is exemplified by human monkeypox, as evidenced increase in reported endemic imported cases over past decades.
Crimean-Congo hemorrhagic fever (CCHF) is a World Health Organization prioritized disease because its broad distribution and severity of make it global health threat. Despite advancements in preclinical vaccine development for CCHF virus (CCHFV), including multiple platforms targeting antigens, clear definition the adaptive immune correlates protection lacking. Levels neutralizing antibodies vaccinated animal models do not necessarily correlate with protection, suggesting that cellular...
ABSTRACT Burkholderia cepacia is an important opportunistic human pathogen that affects immunocompromised individuals, particularly cystic fibrosis (CF) patients. Colonization of the lungs a CF patient by B. can lead not only to decline in respiratory function but also acute systemic infection, such as bacteremia. We have previously demonstrated clinical isolate , strain J2315, invade and survive within cultured epithelial cells. In order further characterize mechanisms invasion we screened...
Crimean-Congo hemorrhagic fever (CCHF) is the most medically important tick-borne viral disease of humans and tuberculosis leading cause death worldwide by a bacterial pathogen. These two diseases overlap geographically, however, concurrent infection CCHF virus (CCHFV) with mycobacterial has not been assessed nor ability to persist long-term sequela in primate model. In this study, we compared progression diverse strains CCHFV recently described cynomolgus macaque All animals demonstrated...
The rapid emergence of SARS-CoV-2 has created a global health emergency. While most human disease is mild, some people develop severe, life-threatening disease.
Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen. In cell culture, CCHFV sensed by the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I) molecule and its adaptor mitochondrial antiviral signaling (MAVS) protein. MAVS initiates both type interferon (IFN-I) proinflammatory responses. Here, we studied role plays in infection mice presence absence of IFN-I activity. MAVS-deficient were not susceptible to when was active showed no signs disease. When...
Abstract Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to 40% mortality rate. With no approved medical countermeasures, CCHFV is considered public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets glycoprotein GP38 and protects mice from lethal challenge when administered prophylactically or therapeutically. Here, we reveal the structures of bound human chimeric mAb newly isolated CC5-17 survivor. These mAbs...
Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed alternatives, the most advanced of which modified-vaccinia virus Ankara (MVA). We previously gene-based vaccine, termed 4pox, targets four orthopoxvirus antigens, A33, B5, A27 L1. This protects mice non-human primates from lethal disease. Here, we investigated capacity...
Poxviruses exist as multiple infectious morphogenic forms commonly simplified mature virions (MV) and extracellular (EV). The roles of subtypes related to disease transmission are enigmatic EVs can both cell associated (CEV) or released particles (rCEV) each with potentially unique biochemical properties impacting stability infectivity. In vitro analysis prototypical poxviruses is utilized infer larger conclusions about the in vivo function all EV-like particles. Here we present data...
Poxviruses are double-stranded DNA viruses including relevant zoonotic pathogens with high morbidity and potential biological warfare threats. Although African swine fever virus belongs to the Asfarviridae family is not strictly classified as a Poxviridae member, both fall within same class of Pokkesviricetes that replicate in cytoplasm. Among compounds targeting these viruses, acyclic nucleoside phosphonate (ANP) prodrugs promising inhibitors viral polymerases. However, some limitations...