A5009561892- Influenza Virus Research Studies
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Hepatitis B Virus Studies
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- interferon and immune responses
- Respiratory viral infections research
- HIV Research and Treatment
- Hepatitis C virus research
- Cytomegalovirus and herpesvirus research
- Viral gastroenteritis research and epidemiology
- Escherichia coli research studies
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- Immune Response and Inflammation
- Immune responses and vaccinations
- Glycosylation and Glycoproteins Research
- Advanced Electron Microscopy Techniques and Applications
- Immune Cell Function and Interaction
- Virology and Viral Diseases
- Infectious Diseases and Mycology
- Cancer-related Molecular Pathways
- Fungal Infections and Studies
- Melanoma and MAPK Pathways
National Institute of Allergy and Infectious Diseases
2016-2025
National Institutes of Health
2013-2025
Cancer Institute (WIA)
2013
Center for Cancer Research
2011-2013
National Cancer Institute
2011-2013
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2005
University of Alabama at Birmingham
1999-2001
Influenza virus remains a global health threat, with millions of infections annually and the impending threat that strain avian influenza may develop into human pandemic. Despite its importance as pathogen, little is known about structure, in part because intrinsic structural variability (pleiomorphy): primary distinction between spherical elongated particles, but both vary size. Pleiomorphy has thwarted analysis by image reconstruction electron micrographs based on averaging many identical...
A DNA vaccine candidate for Zika The ongoing epidemic in the Americas and Caribbean urgently needs a protective vaccine. Two vaccines composed of genes that encode structural premembrane envelope proteins virus have been tested monkeys. Dowd et al. show two doses given intramuscularly completely protected 17 18 animals against challenge. single low dose was not but did reduce viral loads. Protection correlated with serum antibody neutralizing activity. Phase I clinical trials testing these...
The initial step in HIV-1 infection occurs with the binding of cell surface CD4 to trimeric envelope glycoproteins (Env), a heterodimer transmembrane glycoprotein (gp41) and (gp120). design soluble versions Env that display structural functional properties similar those observed on intact viruses is highly desirable from viewpoint designing immunogens could be effective as vaccines against HIV/AIDS. Using cryoelectron tomography combined subvolume averaging, we have analyzed structure SOSIP...
Rapid antigenic variation of HA, the major virion surface protein influenza A virus, remains principal challenge to development broader and more effective vaccines. Some regions such as stem region proximal viral membrane, are nevertheless highly conserved across strains among most subtypes. fundamental question in vaccine design is extent which HA on virus accessible broadly neutralizing antibodies. Here we report 3D structures derived from cryoelectron tomography intact 2009 H1N1 pandemic...
Abstract Influenza virus infects millions of people annually and can cause global pandemics. Hemagglutinin (HA) is the primary component commercial influenza vaccines (CIV), antibody titer to HA a correlate protection. Continual antigenic variation requires that CIVs are reformulated yearly. Structural organization complexes have not previously been correlated with induction broadly reactive antibodies, yet CIV formulations vary in how organized. Using electron microscopy study four current...
Abstract Negative‐stain transmission electron microscopy (EM) is a technique that has provided nanometer resolution images of macromolecules for about 60 years. Developments in cryo‐EM image processing have maximized the information gained from averaging large numbers particles. These developments can now be applied back to negative‐stain analysis ascertain domain level molecular structure (10 20 Å) more quickly and efficiently than possible by atomic cryo‐EM. Using uranyl acetate stained...
Ribonucleoprotein (RNP) complexes of influenza viruses are composed multiple copies the viral nucleoprotein (NP) that can form filamentous supra-structures. RNPs package distinct genomic RNA segments different lengths into pleomorphic virions. also function in transcription and replication. Different RNP have varying lengths, but all must be incorporated virions during assembly then released entry for productive infection cycles. structures serve varied functions replication cycle, therefore...
Introduction Disseminated coccidioidomycosis (DCM) is a serious illness with significant morbidity and mortality, especially in patients impaired host defense mechanisms interferon-gamma (IFN-gamma)/interleukin-12 STAT3 axes. With standard treatments, these often require prolonged, sometimes lifelong, antifungal therapy, which are not curative. The therapeutic benefits of adjunctive IFN-gamma DCM remain unclear. Methods We conducted retrospective chart review treated at our institutions...
ABSTRACT We describe cryo-electron microscopic studies of the interaction between ectodomain trimeric HIV-1 envelope glycoprotein (Env) and Z13e1, a broadly neutralizing antibody that targets membrane-proximal external region (MPER) gp41 subunit. show Z13e1-bound Env displays an open quaternary conformation similar to CD4-bound conformation. Our results support idea MPER-directed antibodies, such as block viral entry by interacting with at step after CD4 activation.
Abstract Influenza virus continues to be a major health problem due the continually changing immunodominant head regions of surface glycoprotein, hemagglutinin (HA). However, some emerging vaccine platforms designed by biotechnology efforts, such as recombinant influenza virus-like particles (VLPs) have been shown elicit protective antibodies antigenically different viruses. Here, using biochemical analyses and cryo-electron microscopy methods coupled image analysis, we report composition 3D...
Abstract Immunoelectron microscopy is a powerful technique for identifying viral antigens and determining their structural localization organization within vaccines viruses. While traditional negative staining transmission electron provides information, identity of components sample may be confounding. allows identification visualization relative positions particulate sample. This simple qualitative analysis samples including whole virus, components, viral‐like particles. article describes...
Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern pandemic threat due continually changing antigenic regions surface glycoprotein, hemagglutinin (HA). One emerging strategy for development more efficacious universal is structure-guided design nanoparticles that display conserved HA, such as stem. Using H1 HA subtype establish proof concept, we found tandem copies an alpha-helical fragment from stem region (helix-A)...
ABSTRACT Influenza virus afflicts millions of people worldwide on an annual basis. There is ever-present risk that animal viruses will cross the species barrier to cause epidemics and pandemics resulting in great morbidity mortality. Zoonosis outbreaks, such as H7N9 outbreak, underscore need better understand molecular organization viral immunogens, recombinant influenza hemagglutinin (HA) proteins, used subunit vaccines order optimize vaccine efficacy. Here, using cryo-electron microscopy...
As new vaccine technologies and platforms, such as nanoparticles novel adjuvants, are developed to aid in the establishment of a universal influenza vaccine, studying traditional split/subunit vaccines should not be overlooked. Commercially available typically studied terms A H1 H3 viruses but B need examined well. Thus, there is both understand limitations develop strategies overcome those limitations, particularly their ability elicit cross-reactive antibodies co-circulating Victoria (B-V)...
The evolutionary relationship of retroviruses to the negative-stranded RNA virus superfamily was examined by comparing protein structures. Since structures are more conserved over time than primary sequences, three-dimensional structural comparisons permit identification relationships that were previously undetected. Human immunodeficiency (HIV) and influenza used as representatives groups, proteins with similar functions compared. M1 has membrane- nucleocapsid-binding activities...
While nanoparticle vaccine technology is gaining interest due to the success of vaccines like those for human papillomavirus that based on viral capsid nanoparticles, little information available disassembly and reassembly surface glycoprotein-based nanoparticles. One such particle hepatitis B virus antigen (sAg) exists as Here we show, using biochemical analysis coupled with electron microscopy, sAg requires both reducing agent disrupt intermolecular disulfide bonds, detergent hydrophobic...