A5082944335- Virus-based gene therapy research
- Cervical Cancer and HPV Research
- SARS-CoV-2 and COVID-19 Research
- Viral Infectious Diseases and Gene Expression in Insects
- Viral gastroenteritis research and epidemiology
- interferon and immune responses
- Viral Infections and Vectors
- Biotin and Related Studies
- Virology and Viral Diseases
- Hepatitis B Virus Studies
- Respiratory viral infections research
- Viral Infections and Immunology Research
- Poxvirus research and outbreaks
- CAR-T cell therapy research
- COVID-19 Clinical Research Studies
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Reproductive tract infections research
- Animal Virus Infections Studies
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Arts, Culture, and Music Studies
- Urological Disorders and Treatments
- Zoonotic diseases and public health
- Parasitic Infections and Diagnostics
University of Arizona
2013-2024
University of Chile
2021
BIO5 Institute
2017
University of New Mexico
2007-2009
Rice University
2003-2006
Baylor College of Medicine
2004-2006
Methodist Hospital
2004-2006
Texas Children's Hospital
2004
Houston Methodist
2004
The human papillomavirus (HPV) L2 capsid protein plays an essential role during the early stages of viral infection, but molecular mechanisms underlying its mode action remain obscure. Using a proteomic approach, we have identified adaptor protein, sorting nexin 17 (SNX17) as strong interacting partner HPV L2. This interaction occurs through highly conserved SNX17 consensus binding motif, which is present in majority proteins analysed. mutants defective for interaction, or siRNA ablation...
Unrelated individuals can produce genetically similar clones of antibodies, known as public clonotypes, which have been seen in responses to different infectious diseases, well healthy individuals. Here we identify 37 clonotypes memory B cells from convalescent survivors severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or plasmablasts an individual after vaccination with mRNA-encoded spike protein. We 29 including recognizing the receptor-binding domain (RBD) protein S1...
ABSTRACT In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology paramount frameworks should be reviewed periodically. Changes made with care, however, to avoid impeding science that essential for rapidly reducing responding pandemic threats as well addressing more common challenges caused by infectious diseases. Decades uniquely positioned US able respond COVID-19 crisis astounding speed, delivering life-saving vaccines...
Papillomaviruses are species-specific and epitheliotropic DNA viruses that cause tumors in their natural hosts. Certain infections with genital human papillomavirus (HPV) types causally related to cervical cancer development. Most papillomaviruses thought infect cells via a clathrin-dependent pathway, yet no studies have determined the entry route permissive host epithelial cells. Employing fluorescently labeled native virions, we tested effects of dominant-negative biochemical inhibitors...
High-risk human papillomaviruses (HPVs) are small nonenveloped DNA viruses with a strict tropism for squamous epithelium. The causative agents of cervical cancer and some head neck cancers, but their differentiation-dependent life cycles have made them difficult to study in simple cell culture. Thus, many aspects early HPV infection remain mysterious. We recently showed the high-risk type 31 (HPV31) enters its natural host via caveola-dependent endocytosis, distinct mechanism from that...
During cellular invasion, human papillomavirus type 16 (HPV16) must transfer its viral genome (vDNA) across the endosomal membrane prior to accumulation at nuclear PML bodies for establishment of infection. After uptake, capsid likely undergoes pH-dependent disassembly within endo-/lysosomal compartment, thereby exposing hidden domains in L2 that facilitate penetration L2/vDNA complexes. In an effort identify regions might physically interact with membranes, we have subjected sequence...
Incoming papillomaviruses (PVs) depend on mitotic nuclear envelope breakdown to gain initial access the nucleus for viral transcription and replication. In our previous work, we hypothesized that minor capsid protein L2 of PVs tethers incoming vDNA chromosomes direct them into nascent nuclei. To re-evaluate how dynamic recruitment cellular occurs specifically during prometaphase, developed a quantitative, microscopy-based assay measuring degree chromosome L2-EGFP. Analyzing various HPV16...
The human papillomavirus type 16 (HPV16) L2 protein acts as a chaperone to ensure that the viral genome (vDNA) traffics from endosomes trans-Golgi network (TGN) and eventually nucleus, where HPV replication occurs. En route L2/vDNA complex must translocate across limiting intracellular membranes. details of this critical process remain poorly characterized. We have developed system based on subcellular compartmentalization enzyme BirA its cognate substrate detect membrane translocation...
Neuropilin-1 (NRP-1) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth and angiogenesis. In addition to role in cancer, NRP-1 reported entry point several viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of disease 2019 (COVID-19). The furin cleavage product SARS-CoV-2 Spike protein takes advantage vascular endothelial factor A (VEGF-A) binding site on which accommodates polybasic stretch ending...
Science is humanity's best insurance against threats from nature, but it a fragile enterprise that must be nourished and protected. The preponderance of scientific evidence indicates natural origin for SARS-CoV-2. Yet, the theory SARS-CoV-2 was engineered in escaped lab dominates media attention, even absence strong evidence. We discuss how resulting anti-science movement puts research community, research, pandemic preparedness at risk.
Development of cell-targeting vectors is an important focus for gene therapy. While some ligands can be genetically inserted into virus capsid proteins cell targeting, many ligands, this approach disrupt either ligand function or vector function. To address problem adenovirus type 5 vectors, the fiber protein was fused to a biotin acceptor peptide (BAP). Adenovirus particles bearing BAP were metabolically biotinylated during production by endogenous ligase in 293 cells produce covalently...
Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded reduce this disease burden with vaccines antivirals. Despite long history, COVID-19 pandemic unprecedented attention field of virology. Some is focused on concern about safe conduct human pathogens. A small but vocal group individuals seized upon these concerns - conflating legitimate questions...
While genetic modification of adenoviral vectors can produce with modified tropism, incorporation targeting peptides/proteins into the structural context virion also result in destruction ligand or integrity. To combat this problem, we have developed a versatile system using metabolically biotinylated bearing fiber proteins. These been demonstrated to be useful as platform for avidin-based screening and vector by conjugating ligands virus high-affinity tetrameric avidin (Kd = 10−15 M). The...
Background Minor capsid protein L2 performs an indispensable but uncharacterized role in human papillomavirus infections. A neutralizing B cell epitope has recently been mapped to the N-terminus of HPV16 L2, residues 17–36, and exposure this region implicated translocation incoming virions from endo/lysosomal compartment cellular cytoplasm. Here we examine redox state Cys22 Cys28 two highly conserved cysteines located within epitope. We also investigate infectivity containing single double...
ABSTRACT Despite an abundance of evidence supporting important role for the cleavage minor capsid protein L2 by cellular furin, direct capsid-associated during human papillomavirus 16 (HPV16) infection remains poorly characterized. The conserved site, close to N terminus, confounds observation and quantification small product SDS-PAGE. To overcome this difficulty, we increased size shift fusing a compact domain, Propionibacterium shermanii transcarboxylase domain (PSTCD), terminus L2....
Oncogenic human papillomaviruses (HPVs) replicate in differentiating epithelium, causing 5% of cancers worldwide. Like most other DNA viruses, HPV infection initiates after trafficking viral genome (vDNA) to host cell nuclei. Cells possess innate surveillance pathways detect microbial components or physiological stresses often associated with infections. One these pathways, cGAS/STING, induces IRF3-dependent antiviral interferon (IFN) responses upon detection cytosolic DNA. Virion-associated...
ABSTRACT Cell invasion by human papillomavirus type 16 (HPV16) is a complex process relying on multiple host cell factors. Here we describe an investigation into the role of cellular protein disulfide isomerases (PDIs) studying effects commonly used PDI inhibitor bacitracin HPV16 infection. Bacitracin caused unusual time-dependent opposing effect viral Enhanced binding and entry were observed at early times infection, while inhibition was later postentry. rapidly taken up cells colocalized...
Abstract Mitosis induces cellular rearrangements like spindle formation, Golgi fragmentation, and nuclear envelope breakdown. Similar to certain retroviruses, delivery during entry of human papillomavirus (HPV) genomes is facilitated by mitosis, which minor capsid protein L2 tethers viral DNA mitotic chromosomes. However, the mechanism genome tethering condensed chromosomes barely understood. It unclear, proteins facilitate this process or how regulated. This work identifies crucial...