A5065527545- Viral Infections and Outbreaks Research
- Hepatitis B Virus Studies
- SARS-CoV-2 and COVID-19 Research
- Mosquito-borne diseases and control
- Influenza Virus Research Studies
- Lipid Membrane Structure and Behavior
- COVID-19 epidemiological studies
- interferon and immune responses
- Disaster Response and Management
- Virology and Viral Diseases
- Viral gastroenteritis research and epidemiology
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- Viral Infections and Vectors
- Animal Virus Infections Studies
- Bacillus and Francisella bacterial research
- Neurological Disease Mechanisms and Treatments
- Erythrocyte Function and Pathophysiology
- Neonatal Respiratory Health Research
- Vibrio bacteria research studies
- Immune cells in cancer
- Immune Cell Function and Interaction
- Blood properties and coagulation
- Neurological Disorders and Treatments
- Hemoglobinopathies and Related Disorders
Purdue University West Lafayette
2018-2024
University of Notre Dame
2016-2017
Midwestern University
2015
We lack a mechanistic understanding of aging-mediated changes in mitochondrial bioenergetics and lipid metabolism that affect T cell function. The bioactive sphingolipid ceramide, induced by aging stress, mediates mitophagy death; however, the aging-related roles ceramide regulating function remain unknown. Here, we show activated cells isolated from mice have elevated C14/C16 accumulation mitochondria, generated synthase 6, leading to mitophagy/mitochondrial dysfunction. Mechanistically,...
Measles virus, Nipah and multiple other paramyxoviruses cause disease outbreaks in humans animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of are available, we lack the clear understanding how viral proteins interact with membrane lipids to mediate egress that needed guide antiviral design. Here, reveal associate phosphatidylserine phosphatidylinositol...
Article12 September 2022Open Access Source DataTransparent process Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding Monica L Husby Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, IN, USA Institute Inflammation, Immunology and Infectious Disease (PI4D), Contribution: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Writing - original draft, review editing...
The Ebola virus matrix protein VP40 is responsible for the formation of viral by localizing at inner leaflet human plasma membrane (PM). Various lipid types, including PI(4,5)P2 (i.e. PIP2) and phosphatidylserine (PS), play active roles in this process. Specifically, negatively charged headgroups both PIP2 PS interact with basic residues stabilize it surface, allowing eventual egress. Phosphatidic acid (PA), resulting from enzyme phospholipase D (PLD), also known to an role development. In...
The Ebola virus protein VP40 is a transformer that possesses an extraordinary ability to accomplish multiple functions by transforming into various oligomeric conformations. disengagement of the C-terminal domain (CTD) from N-terminal (NTD) crucial step in conformational transformations dimeric form hexameric or octameric ring structure. Here, we use molecular dynamics (MD) simulations investigate and roles interdomain interactions are important for domain-domain association dissociation,...
Marburg virus (MARV) is a lipid-enveloped harboring negative-sense RNA genome, which has caused sporadic outbreaks of viral hemorrhagic fever in sub-Saharan Africa. MARV assembles and buds from the host cell plasma membrane where matrix protein (mVP40) dimers associate with anionic lipids at inner leaflet undergo dynamic extensive self-oligomerization into structural layer. The layer confers virion filamentous shape stability but how modulate mVP40 oligomerization mostly unknown. Using vitro...
Ebola virus (EBOV) infection is threatening human health, especially in Central and West Africa. Limited clinical trials the requirement of biosafety level-4 laboratories hinder experimental work to advance our understanding EBOV evaluation treatment. In this work, we use a computational model study assembly budding process evaluate effect fendiline on these processes context fluctuating host membrane lipid levels. Our results demonstrate for first time that VP40 filaments may follow...
Ebola virus (EBOV) infections continue to pose a global public health threat, with high mortality rates and sporadic outbreaks in Central Western Africa. A quantitative understanding of the key processes driving EBOV assembly budding could provide valuable insights inform drug development. Here, we use computational model evaluate matrix assembly. Our focuses on kinetics VP40, protein EBOV, its interaction phosphatidylserine (PS) host cell membrane. It has been shown that mammalian cells...
Marburg virus (MARV) is a lipid-enveloped negative sense single stranded RNA virus, which can cause deadly hemorrhagic fever. MARV encodes seven proteins, including VP40 (mVP40), matrix protein that interacts with the cytoplasmic leaflet of host cell plasma membrane. traffics to membrane inner leaflet, where it assembles facilitate budding viral particles. multifunctional several proteins and lipids complete replication cycle, but many these interactions remain unknown or are poorly...
Marburg virus (MARV) is a lipid-enveloped negative sense single stranded RNA virus, which can cause deadly hemorrhagic fever. MARV encodes seven proteins, including VP40 (mVP40), matrix protein that interacts with the cytoplasmic leaflet of host cell plasma membrane. traffics to membrane inner leaflet, where it assembles facilitate budding viral particles. multifunctional several proteins and lipids complete replication cycle, but many these host-interactions remain unknown or are poorly...
The most prolonged and fatal outbreak of the Ebola virus (EBOV) occurred in 2014, claiming lives thousands. Although more than 40 years have passed since initial discovery EBOV, there are still no available treatments with FDA approval. Clinical case studies from human survivors highlighted that a hallmark survival is measurable immune response against specific viral proteins, such as VP40. VP40, canonical mediator EBOV budding. Therefore, slowing down propagation through inhibiting...
Abstract Ebola virus (EBOV) infection is threatening human health, especially in Central and West Africa. Limited clinical trials the requirement of biosafety level-4 (BSL-4) laboratories hinders experimental work to advance our understanding EBOV evaluation treatment. In this work, we use a computational model study assembly budding process evaluate effect fendiline on these processes. Our results indicate that VP40 filaments may follow nucleation-elongation theory, as it critical maintain...
Abstract Phosphatidylserine (PS) has been shown to be a critical lipid factor in the assembly and spread of numerous enveloped viruses. Here, we describe ability Ebola virus (EBOV) matrix protein eVP40 induce clustering PS promote viral budding vitro , as well an FDA approved drug, fendiline, reduce subsequently reducing entry. To gain mechanistic insight into fendiline inhibition EBOV replication, multiple assays were employed including imaging, entry assays. Fendiline reduced content...
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Endothelin B (ETB) receptor agonist, IRL-1620 administered at 2, 4, 6 hr post-cerebral ischemia, has been shown to significantly aid in neuroprotection and neurovascular remodeling normal rats. The incidence of type 2 diabetes mellitus (diabetes) is on the rise it can be expected that there will an upsurge associated diseases, such as ischemic stroke patients with diabetes. present study was conducted determine efficacy effect (non-diabetic) diabetic rats following cerebral ischemia induced...
In 2014, an international public health emergency was declared when Ebola virus outbreak claimed the lives of thousands, resulting in most fatal, widespread and prolonged recorded history. Although 40 years have passed since initial outbreak, numerous vaccines post‐exposure therapeutics entered phase I, II III clinical trials, yet all failed to gain FDA approval. Clinical case studies highlighted that a measurable immune response is key difference between fatal cases survivors infections....
Summary Marburg virus major matrix protein (mVP40) dimers associate with anionic lipids at the plasma membrane and undergo a dynamic extensive self-oligomerization into structural layer which confers virion shape stability. Using myriad of in vitro cellular techniques, we present mVP40 assembly model highlighting two distinct oligomerization interfaces (N-terminal domain (NTD) C-terminal (CTD)) mVP40. Cellular studies NTD CTD interface mutants demonstrated importance each through trafficking...
Abstract Plasma membrane (PM) domains and order phases have been shown to play a key role in the assembly, release, entry of several lipid-enveloped viruses. In present study, we provide mechanistic understanding Ebola virus (EBOV) matrix protein VP40 interaction with PM lipids their effect on oligomerization, crucial step for viral assembly budding. formation is sufficient induce changes fluidity. We demonstrate that distance between lipid headgroups, fatty acid tail saturation two leaflets...
Abstract Ebola virus (EBOV) infections continue to pose a global public health threat, with high mortality rates and sporadic outbreaks in Central Western Africa. A quantitative understanding of the key processes driving EBOV assembly budding could provide valuable insights inform drug development. Here we used computational model evaluate matrix assembly. Our focused on kinetics VP40, protein EBOV, its interaction phosphatidylserine (PS) host cell membrane. Human cells transfected...
Abstract Measles virus, Nipah and multiple other paramyxoviruses cause disease outbreaks in humans animals worldwide. The paramyxovirus matrix (M) protein mediates virion assembly budding from host cell membranes. M is thus a key target for antivirals, but few high-resolution structures of are available, we lack the clear understanding how viral proteins interact with membrane lipids to mediate egress needed guide antiviral design. Here, reveal that associate phosphatidylserine...