A5033840109- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Mosquito-borne diseases and control
- Viral gastroenteritis research and epidemiology
- interferon and immune responses
- Bacteriophages and microbial interactions
- Virology and Viral Diseases
- Animal Disease Management and Epidemiology
- Viral Infections and Immunology Research
- Data-Driven Disease Surveillance
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Plant Virus Research Studies
- Respiratory viral infections research
- Hepatitis C virus research
- Cytomegalovirus and herpesvirus research
- Insect symbiosis and bacterial influences
- COVID-19 epidemiological studies
- Malaria Research and Control
- Health, Environment, Cognitive Aging
- Scientific Computing and Data Management
- Virus-based gene therapy research
- RNA regulation and disease
- Cardiovascular Health and Risk Factors
- Genetics, Bioinformatics, and Biomedical Research
National Institute of Allergy and Infectious Diseases
2022-2025
National Institutes of Health
2022-2025
J. Craig Venter Institute
2014-2021
American Type Culture Collection
2017-2019
Icahn School of Medicine at Mount Sinai
2010-2018
University of North Carolina at Chapel Hill
2005-2018
Dengue virus (DENV) is a pathogen with high impact on human health. It replicates in wide range of cells involved the immune response. To efficiently infect humans, DENV must evade or inhibit fundamental elements innate system, namely type I interferon circumvents host response by expressing proteins that antagonize cellular immunity. We have recently documented inhibition IFN production proteolytic activity NS2B3 protease complex monocyte derived dendritic (MDDCs). In present report we...
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that causally linked to severe neonatal birth defects, including microcephaly, and associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are important cell type during infection by multiple flaviviruses, dengue virus, West Nile Japanese encephalitis yellow fever virus. Despite this, the interplay between ZIKV DCs remains poorly defined. Here, we found human supported productive a contemporary Puerto Rican isolate...
ABSTRACT Mosquito-borne alphaviruses are a significant cause of both encephalitic and arthritic disease in humans worldwide. In contrast to the alphaviruses, pathogenesis alphavirus-induced is not well understood. Utilizing mouse model Ross River virus (RRV) disease, we found that primary targets RRV infection bone, joint, skeletal muscle tissues hind limbs outbred CD-1 mice adult C57BL/6J mice. Moreover, histological analyses demonstrated resulted severe inflammation these tissues....
Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers preformed nucleocapsids, but their biological significance has been debated, and they have suggested to be aggregates viral proteins without any further function. However, recent data for other viruses that produce similar structures inclusion might involved genome replication transcription. In order study filovirus bodies, we fused mCherry the polymerase L, which is found bodies. The...
During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free to provide the polymerase access template. In addition, newly synthesized NP must be prevented from indiscriminately binding noncognate RNAs. Here, we investigate molecular bases for these critical processes. We identify intrinsically disordered peptide derived EBOV VP35 (NPBP, residues 20-48) that binds with high affinity specificity, inhibits oligomerization,...
Kelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription nuclear (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 accumulation, binding to antioxidant response elements (AREs), of cytoprotective genes. Marburg virus (MARV) zoonotic pathogen likely uses bats as reservoir hosts. We demonstrate MARV VP24 (mVP24) binds the Kelch domain either human...
Enterovirus D68 (EV-D68) has historically been associated with respiratory illnesses. However, in the summers of 2014 and 2016, EV-D68 outbreaks coincided a spike polio-like acute flaccid myelitis/paralysis (AFM/AFP) cases. This raised concerns that could be causative agent AFM during these recent outbreaks. To assess potential neurotropism EV-D68, we utilized neuroblastoma-derived neuronal cell line SH-SY5Y as culture model to determine if differential infection is observed for different...
Filoviruses, marburgvirus (MARV) and ebolavirus (EBOV), are causative agents of highly lethal hemorrhagic fever in humans. MARV EBOV share a common genome organization but show important differences replication complex formation, cell entry, host tropism, transcriptional regulation, immune evasion. Multifunctional filoviral viral protein (VP) 35 proteins inhibit innate responses. Recent studies suggest double-stranded (ds)RNA sequestration is potential mechanism that allows VP35 to...
Viral protein 35 (VP35), encoded by filoviruses, is a multifunctional dsRNA binding that plays important roles in viral replication, innate immune evasion, and pathogenesis. The nature of these proteins also presents opportunities to develop countermeasures target distinct functional regions. However, validation the establishment therapeutic approaches toward such proteins, particularly for nonenzymatic targets, are often challenging. Our previous work on filoviral VP35 defined conserved...
ABSTRACT Since the India and Indian Ocean outbreaks of 2005 2006, global distribution chikungunya virus (CHIKV) locations epidemics have dramatically shifted. First, lineage (IOL) caused sustained in has radiated to many other countries. Second, Asian frequent Pacific islands 2013 was introduced into Caribbean, followed by rapid spread nearly all neotropics. Further, CHIKV epidemics, as well exported cases, been reported central Africa after a long period perceived silence. To understand...
Suppression of innate immune responses during filoviral infection contributes to disease severity. Ebola (EBOV) and Marburg (MARV) viruses each encode a VP35 protein that suppresses RIG-I-like receptor signaling interferon-α/β (IFN-α/β) production by several mechanisms, including direct binding double stranded RNA (dsRNA). Here, we demonstrate in cell culture, MARV results greater upregulation IFN as compared EBOV infection. This correlates with differences the efficiencies which VP35s...
Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5′ and 3′ untranslated regions (UTRs) present the seven viral transcriptional units. To date, specific functions have not been assigned these UTRs. With reporter assays, we demonstrated that Zaire ebolavirus (EBOV) 5′-UTRs lack internal ribosomal entry site function. However, do differentially regulate cap-dependent translation when placed...
Deep sequencing of RNAs produced by Zaire ebolavirus (EBOV) or the Angola strain Marburgvirus (MARV-Ang) identified novel viral and cellular mechanisms that diversify coding noncoding sequences mRNAs genomic RNAs. We previously undescribed sites within EBOV MARV-Ang where apparent cotranscriptional editing has resulted in addition non-template-encoded residues glycoprotein (GP) mRNA, nucleoprotein (NP) polymerase (L) such translation products could be produced. Further, we found...
Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified bats; however, the viruses could not be cultured. This discovery aroused great interest understanding evolutionary history and pandemic potential bat-influenza. Using synthetic genomics, we unable rescue wild type bat virus, but a modified bat-influenza virus that had HA NA coding regions replaced with those...
Dendritic cells (DCs) are an important early target cell for many mosquito-borne viruses, and in cases mosquito-cell-derived arboviruses more efficiently infect DCs than viruses derived from mammalian cells. However, whether differ mammalian-cell-derived their ability to induce antiviral responses the infected dendritic has not been evaluated. In this report, alphaviruses, which that cause diseases ranging encephalitis arthritis, were used determine grown mosquito differed type I interferon...
ABSTRACT The ebolavirus (EBOV) VP35 protein binds to double-stranded RNA (dsRNA), inhibits host alpha/beta interferon (IFN-α/β) production, and is an essential component of the viral polymerase complex. Structural studies C-terminal IFN inhibitory domain (IID) identified specific structural features, including a central basic patch hydrophobic pocket, that are important for dsRNA binding inhibition. Several other conserved residues bordering separate cluster residues, called first patch,...
Antigen-presenting cells (APCs) are critical targets of Ebola virus (EBOV) infection in vivo. However, the susceptibility monocytes to is controversial. Studies indicate productive monocyte infection, and yet also reported be resistant EBOV GP-mediated entry. In contrast, monocyte-derived macrophages dendritic permissive for both entry replication. Here, freshly isolated demonstrated indeed refractory binds monocytes, delayed occurs during differentiation. Cultured spontaneously downregulate...
Abstract Type III IFNs are important mediators of antiviral immunity. IFN-λ4 is a unique type IFN because it produced only in individuals who carry dG allele genetic variant rs368234815-dG/TT. Counterintuitively, those can produce IFN-λ4, an cytokine, also less likely to clear hepatitis C virus infection. In this study, we searched for functional properties that might explain its negative effect on clearance. We used fresh primary human hepatocytes (PHHs) treated with recombinant or infected...
The 50-year-old Aedes albopictus C6/36 cell line is a resource for the detection, amplification, and analysis of mosquito-borne viruses including Zika, dengue, chikungunya. derived from an unknown number larvae unspecified strain mosquitoes. Toward improved utility research in virus transmission, we present annotated assembly genome.The genome has largest contig N50 (3.3 Mbp) any mosquito assembly, presents sequences both haplotypes most diploid genome, reveals independent null mutations...
<ns4:p><ns4:bold>Background:</ns4:bold>The tick cell line ISE6, derived from<ns4:italic>Ixodes scapularis</ns4:italic>, is commonly used for amplification and detection of arboviruses in environmental or clinical samples.</ns4:p><ns4:p><ns4:bold>Methods:</ns4:bold>To assist with sequence-based assays, we sequenced the ISE6 genome single-molecule, long-read technology.</ns4:p><ns4:p><ns4:bold>Results:</ns4:bold>The draft assembly appears near complete based on gene content analysis, though it...