A5070143056- Mosquito-borne diseases and control
- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- Autophagy in Disease and Therapy
- HIV Research and Treatment
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Virology and Viral Diseases
- Hepatitis B Virus Studies
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- Extracellular vesicles in disease
- interferon and immune responses
- Respiratory viral infections research
- Insect symbiosis and bacterial influences
- RNA regulation and disease
- Viral Infectious Diseases and Gene Expression in Insects
- Epigenetics and DNA Methylation
- Influenza Virus Research Studies
- SARS-CoV-2 detection and testing
- Barrier Structure and Function Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- COVID-19 epidemiological studies
- Toxoplasma gondii Research Studies
University of Alabama at Birmingham
2020-2025
University of Iowa
2012-2021
University of Pittsburgh
2015-2020
Children's Hospital of Pittsburgh
2017-2020
Children's Healthcare of Atlanta
2011
Emory University
2011
Northwestern University
2011
Czech Academy of Sciences, Institute of Microbiology
2011
The glycoproteins (GP) of enveloped viruses facilitate entry into the host cell by interacting with specific cellular receptors. Despite extensive study, a receptor for deadly filoviruses Ebolavirus and Marburgvirus has yet to be identified characterized. Here, we show that T-cell Ig mucin domain 1 (TIM-1) binds binding Zaire Ebola virus (EBOV) glycoprotein, ectopic TIM-1 expression in poorly permissive cells enhances EBOV infection 10- 30-fold. Conversely, reduction cell-surface RNAi...
The endoplasmic reticulum (ER) is exploited by several diverse viruses during their infectious life cycles. Flaviviruses, including dengue virus (DENV) and Zika (ZIKV), utilize the ER as a source of membranes to establish replication organelles facilitate assembly eventual maturation along secretory pathway. To maintain normal homeostasis, host cells have evolved highly efficient processes dynamically regulate ER, such through reticulophagy, selective form autophagy that leads degradation....
ABSTRACT Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, glycan cap and mucin-like domain (MLD). only N-linked glycans, whereas MLD both N- O-linked glycans. Site-directed mutagenesis was performed on EBOV to systematically disrupt sites gain an understanding their role in GP structure function. All 15 N-glycosylation could be removed without...
With properties such as stability to long-term storage and amenability repetitive use, nucleic acid aptamers are compatible with many sensing/transducing platforms intended for use in remote locations. Sensors these important quickly identifying ebolavirus outbreaks, which frequently start locations that lack sophisticated equipment. Soluble glycoprotein (sGP), an excellent biomarker ebolaviruses, is produced from the same gene GP1,2 decorates surface of viral particle secreted abundance...
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Abstract Orthoflaviviruses are small, enveloped, positive-sense RNA viruses that cause over 500 million infections globally each year for which there no antiviral treatments. The viral protease is an attractive target therapeutics due to its critical functions throughout infection. Many studies have reported on the structure, function, and importance of orthoflavivirus proteases; However, molecular determinants cleavage intracellular substrates by proteases how these factors affect fitness...
Interferon stimulated genes (ISGs) target viruses at various stages of their infectious life cycles, including the earliest stage viral entry. Here we identify ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2) as a gene upregulated by type I IFN treatment in STAT1-dependent manner. ADAP2 functions GTPase-activating protein (GAP) for Arf6 and binds to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) PI(3,4)P2. We show that overexpression suppresses dengue virus (DENV)...
The blood-brain barrier (BBB) comprises the foremost protective in brain and is composed part of a layer microvascular endothelial cells that line capillaries surrounding brain. Here, we describe human three-dimensional (3-D) cell-based model BBB endothelium recapitulates properties these vivo, including physiologically relevant transcriptional profiles, capacity to induce potent antimicrobial innate immune signaling, ability resist infection by diverse RNA viruses, members enterovirus...
Macroautophagy/autophagy is a conserved catabolic process that promotes survival during stress. Autophagic dysfunction associated with pathologies such as cancer and neurodegenerative diseases. Thus, autophagy must be strictly modulated at multiple levels (transcriptional, post-transcriptional, translational post-translational) to prevent deregulation. Relatively little known about the post-transcriptional control of autophagy. Here we report exoribonuclease Xrn1/XRN1 functions negative...
Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show another BPIFB family, BPIFB6, functions as a positive regulator CVB, and other enterovirus, by controlling secretory pathway trafficking Golgi complex morphology. We similar to BPIFB3, BPIFB6 localizes exclusively ER, where...
Flaviviruses, including dengue virus (DENV) and Zika (ZIKV), rely heavily on the availability of endoplasmic reticulum (ER) membranes throughout their life cycle, degradation ER restricts flavivirus replication. Accordingly, DENV ZIKV restrict turnover by protease-mediated cleavage reticulophagy regulator 1 (RETREG1), also known as FAM134B, an autophagy receptor responsible for targeted sheet degradation. Given that induction may play important role in replication, antiviral RETREG1 suggests...
The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA approved. To expand options potentially available, we assessed protection conferred an EBOV composed of vesicular stomatitis pseudovirions that lack native G glycoprotein (VSVΔG) and bear (GP). These mediate single round infection. Both single-dose prime/boost vaccination regimens protected mice...
Background. N-linked glycosylation is a common posttranslational modification found on viral glycoproteins (GPs) and involved in promoting expression, cellular attachment, protection from proteases, antibody evasion. The GP subunit GP2 of filoviruses contains 2 completely conserved sites (NGSs) at N563 N618, suggesting that they have been maintained through selective pressures.
Flaviviruses represent a large group of globally significant, insect-borne pathogens. For many these viruses, there is lack antivirals and vaccines. Thus, need to continue the development tools further advance our efforts combat pathogens, including reverse genetics techniques. Traditionally, methods for flaviviruses rely on producing infectious RNA from in vitro transcription reactions followed by electroporation or transfection into permissive cell lines. However, production Zika virus has...
Autophagy is a degradative cellular pathway that targets cytoplasmic contents and organelles for turnover by the lysosome. Various autophagy pathways play key roles in clearance of viral infections, many families viruses have developed unique methods avoiding degradation. Some positive-stranded RNA viruses, such as enteroviruses flaviviruses, usurp autophagic to promote their own replication. We previously identified endoplasmic reticulum (ER)-localized protein BPIFB3 an important negative...
Infection by flaviviruses leads to dramatic remodeling of the endoplasmic reticulum (ER). Viral replication occurs within virus-induced vesicular invaginations in ER membrane. A hallmark flavivirus infection is expansion membrane which can be observed at specific time points post infection. However, this process has not been effectively visualized living cells throughout course single cell resolution. In study, we developed a plasmid-based reporter system monitor and simultaneous...
Infection by human astrovirus (HAstV), a small, positive-strand RNA virus, is major cause of gastroenteritis and has been implicated in an increasing number severe, sometimes fatal, neurological diseases since 2008. Currently, there are no vaccines or antiviral treatments available to treat HAstV infection. An attractive target for therapeutics the viral protease due its essential functions throughout However, molecular mechanisms protease, nonstructural protein 1a/3 (nsp1a/3), poorly...
Enteroviruses manipulate host membranes to form replication organelles, which concentrate viral and factors allow for efficient replication. However, this process has not been well-studied in living cells throughout the course of infection. To define dynamic enterovirus membrane remodeling major secretory pathway we have developed plasmid-based reporter systems that utilize protease-dependent release a nuclear-localized fluorescent protein from endoplasmic reticulum (ER) during infection,...
Abstract Autophagy is a degradative cellular pathway that targets cytoplasmic contents and organelles for turnover by the lysosome. Various autophagy pathways play key roles in clearance of viral infections, many families viruses have developed unique methods avoiding degradation. Some positive stranded RNA viruses, such as enteroviruses flaviviruses, usurp autophagic to promote their own replication. We previously identified endoplasmic reticulum-localized protein BPIFB3 an important...