A5074400687- Virus-based gene therapy research
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Viral gastroenteritis research and epidemiology
- Occupational Health and Performance
- RNA and protein synthesis mechanisms
- Parvovirus B19 Infection Studies
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Hepatitis B Virus Studies
- Cervical Cancer and HPV Research
- Bacteriophages and microbial interactions
- Cell death mechanisms and regulation
- Adipose Tissue and Metabolism
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Plant Virus Research Studies
- Immunotherapy and Immune Responses
- DNA Repair Mechanisms
- Cytomegalovirus and herpesvirus research
- HIV Research and Treatment
- DNA and Nucleic Acid Chemistry
- Blood Coagulation and Thrombosis Mechanisms
- Genital Health and Disease
- Urbanization and City Planning
Hormel (United States)
2024-2025
University of Minnesota
2024-2025
Millennium Engineering and Integration (United States)
2019-2023
Pennsylvania State University
2011-2023
University of Rochester
2009-2017
Penn State Milton S. Hershey Medical Center
2011
Clemson University
2010
Pusan National University
2009
Ajou University
2005-2007
City Of Hope National Medical Center
2007
As a para-retrovirus, hepatitis B virus (HBV) is an enveloped with double-stranded (DS) DNA genome that replicated by reverse transcription of RNA intermediate, the pregenomic or pgRNA. HBV assembly begins formation "immature" nucleocapsid (NC) incorporating pgRNA, which converted via within maturing NC to DS genome. Only mature, DNA-containing NCs are and secreted as virions whereas immature containing single-stranded (SS) not enveloped. The current model for selective virion morphogenesis...
Some strains of enterovirus 71 (EV71), but not others, infect leukocytes by binding to a specific receptor molecule: the P-selectin glycoprotein ligand-1 (PSGL-1). We find that single amino acid residue within capsid protein VP1 determines whether EV71 binds PSGL-1. Examination sequences representative revealed PSGL-1-binding viruses had either G or Q at 145 (VP1-145G Q), whereas PSGL-1-nonbinding VP1-145E. Using site-directed mutagenesis we found lost their capacity bind when VP1-145G/Q was...
Significance Precise regulation of chemokine signal is critical for directional migration cells. In the study complex cell behavior, it remains difficult to manipulate activity at precise times and places within living animals, not possible different effects on defined types over a range timescales. Furthermore, given can activate multiple receptors vice versa. Here we developed photoactivatable receptor that induce highly specific signals guide toward light stimulation. This work will...
Rapid mutation rates and correspondingly high levels of intra- interhost diversity are often cited as key features viruses with the capacity for emergence sustained transmission in a new host species. However, most this information comes from studies RNA viruses, relatively little known about evolutionary processes single-stranded DNA (ssDNA) genomes. Here, we provide unique model virus evolution, integrating both long-term global-scale short-term intrahost an ssDNA that emerged to cause...
Enterovirus 71 (EV71) is a picornavirus that causes outbreaks of hand, foot, and mouth disease (HFMD), primarily in the Asia-Pacific area. Unlike coxsackievirus A16, which also HFMD, EV71 induces severe neuropathology leading to high fatalities, especially among children under age 6 years. Currently, no established vaccines or treatments are available against infection. The monoclonal antibody MA28-7 neutralizes only specific strains have conserved glycine at amino acid VP1-145,...
Human papillomavirus 16 (HPV16) is a worldwide health threat and an etiologic agent of cervical cancer. To understand the antigenic properties HPV16, we pursued structural study to elucidate HPV capsids antibody interactions. The cryo-electron microscopy (cryo-EM) structures mature HPV16 particle altered capsid were solved individually as complexes with fragment (Fab) from neutralizing H16.V5. Fitted crystal provided pseudoatomic model virus-Fab complex, which identified precise footprint...
Nanodiscs used as a mock membrane captured picornavirus undergoing global and local changes to enter host cells.
Host antibody responses are key components in the protection of animals against pathogens, yet defining properties viral antigens and induction B cell that result varied still poorly understood. Parvoviruses simple molecular structures display 60 repeated motifs on their capsid surface, rapidly induce strong protect from infection. We recently showed following canine parvovirus infection its natural host, polyclonal response sera contained only two or three dominant antibodies bound epitopes...
Cryo-electron microscopy (cryo-EM) was used to solve the structures of human papillomavirus type 16 (HPV16) complexed with fragments antibody (Fab) from three different neutralizing monoclonals (mAbs): H16.1A, H16.14J, and H263.A2. The structure-function analysis revealed predominantly monovalent binding each Fab capsid interactions that involved multiple loops symmetry related copies major protein. residues identified in Fab-virus interface map a conformational groove on surface capsomer....
Canine parvovirus (CPV) is an important pathogen causing severe diseases in dogs, including acute hemorrhagic enteritis, myocarditis, and cerebellar disease. Cross-species transmission of CPV occurs as a result mutations on the viral capsid surface that alter species-specific binding to host receptor, transferrin receptor type-1 (TfR). The interaction between TfR has been extensively studied, previous analyses have suggested CPV–TfR complex asymmetric. To enhance understanding underlying...
ABSTRACT Enterovirus 71 (EV71) is an important emerging human pathogen with a global distribution and presents disease pattern resembling poliomyelitis seasonal epidemics that include cases of severe neurological complications, such as acute flaccid paralysis. EV71 member the Picornaviridae family, which consists icosahedral, nonenveloped, single-stranded RNA viruses. Here we report structures derived from X-ray crystallography cryoelectron microscopy (cryo-EM) for 1095 strain EV71,...
Abstract RNase MRP is an essential eukaryotic ribonucleoprotein complex involved in the maturation of rRNA and regulation cell cycle. related to ribozyme-based P, but it has evolved have distinct cellular roles. We report a cryo-EM structure S. cerevisiae holoenzyme solved 3.0 Å. describe this 450 kDa complex, interactions between its components, organization catalytic RNA. show that some proteins shared with P undergo unexpected RNA-driven remodeling allows them bind divergent RNAs....
Canine parvovirus (CPV) is a highly contagious pathogen that causes severe disease in dogs and wildlife. Previously, panel of neutralizing monoclonal antibodies (MAb) raised against CPV was characterized. An antibody fragment (Fab) MAb E found to neutralize the virus at low molar ratios. Using recent advances cryo-electron microscopy (cryo-EM), we determined structure complex with Fab 4.1 Å resolution, which allowed de novo building structure. The footprint identified significantly different...
Enterovirus A71 (EV-A71) is a non-polio neurotropic enterovirus with pandemic potential. There are no antiviral agents approved to prevent or treat EV-A71 infections. We here report on the molecular mechanism by which novel class of tryptophan dendrimers inhibits (at low nanomolar high picomolar concentration) replication in vitro. A lead compound series (MADAL385) prevents binding and internalization virus but does not, unlike classical capsid binders, stabilize particle. By means...
Currently, there are only three FDA-approved drugs that inhibit human immunodeficiency virus (HIV) entry-fusion into host cells. The situation is even worse for enterovirus EV71 infection which no antiviral therapies available. We describe here the discovery of potent entry dual inhibitors HIV and EV71. These compounds contain in their structure or four tryptophan (Trp) residues linked to a central scaffold. Critical anti-HIV/EV71 activity presence extra phenyl rings, bearing one two...
The human papillomavirus (HPV) major structural protein L1 composes capsomers that are linked together through interactions mediated by the C terminus to constitute a T=7 icosahedral capsid. H16.U4 is type-specific monoclonal antibody recognizing conformation-dependent neutralizing epitope of HPV thought include terminus. structure 16 (HPV16) complexed with fragments (Fab) was solved cryo-electron microscopy (cryo-EM) image reconstruction. Atomic structures virus and Fab were fitted into...
Abstract Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines antivirals. In support this goal, we map the epitope human monoclonal antibody 9H2 which able neutralize three serotypes poliovirus. Using cryo-EM solve near-atomic structures fragments (Fab) bound capsids 1, 2, 3. The Fab-virus complexes show that Fab interacts with same binding mode for each serotype at angle interaction relative capsid surface. For complexes, find site...
Canine parvovirus (CPV) is a small nonenveloped single-stranded DNA virus that causes serious diseases in dogs worldwide. The original strain of the (CPV-2) emerged during late 1970s due to host range switch similar feline panleukopenia infected another host. had altered capsid receptor and antibody binding sites, with some changes affecting both functions. Further arose when became better adapted or other hosts. Here, we used
Abstract The host injury involved in multiorgan system failure during severe inflammation is mediated, part, by massive infiltration and sequestration of hyperactive neutrophils the visceral organ. A recombinant form human activated protein C (rhAPC) has shown cytoprotective anti-inflammatory functions some clinical animal studies, but direct mechanism not fully understood. Recently, we reported that, endotoxemia polymicrobial peritonitis, integrin VLA-3 (CD49c/CD29) specifically upregulated...