A5031988372- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- SARS-CoV-2 detection and testing
- Influenza Virus Research Studies
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Plant Virus Research Studies
- HIV Research and Treatment
- Diabetes and associated disorders
- Viral gastroenteritis research and epidemiology
- Chromosomal and Genetic Variations
- COVID-19 Clinical Research Studies
- interferon and immune responses
- Advanced biosensing and bioanalysis techniques
- Bacteriophages and microbial interactions
- Antenna Design and Analysis
- Biosensors and Analytical Detection
- Helicobacter pylori-related gastroenterology studies
- Respiratory viral infections research
- Viral Infections and Outbreaks Research
- Immune Cell Function and Interaction
- Clostridium difficile and Clostridium perfringens research
- Herpesvirus Infections and Treatments
- Biochemical and Structural Characterization
- Toxin Mechanisms and Immunotoxins
University of Pittsburgh
2021-2025
Harvard University
2018-2024
UPMC Hillman Cancer Center
2021-2023
University of Pittsburgh Medical Center
2022
Boston VA Research Institute
2021
Zoonotic pandemics, such as that caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can follow the spillover of animal viruses into highly susceptible human populations. The descendants these have adapted to host and evolved evade immune pressure. Coronaviruses acquire substitutions more slowly than other RNA viruses. In spike glycoprotein, we found recurrent deletions overcome this slow substitution rate. Deletion variants arise in diverse genetic geographic...
Incorporating TLR9-inhibitory sequences in the AAV vector genome inhibits immunogenicity and enhances transgene expression multiple animal models.
Abstract Zoonotic pandemics, like that caused by SARS-CoV-2, can follow the spillover of animal viruses into highly susceptible human populations. Their descendants have adapted to host and evolved evade immune pressure. Coronaviruses acquire substitutions more slowly than other RNA viruses, due a proofreading polymerase. In spike glycoprotein, we find recurrent deletions overcome this slow substitution rate. Deletion variants arise in diverse genetic geographic backgrounds, transmit...
A panzootic of highly pathogenic avian influenza (HPAI) H5N1 viruses from clade 2.3.4.4b has triggered a multistate outbreak in United States dairy cattle and an unknown number human infections. HPAI are handled specialized biocontainment facilities. Ethical considerations limit certain experimental evolution experiments aimed at assessing viral resistance to potential therapeutics. We have developed replicating recombinant vesicular stomatitis virus (rVSV) where we replaced its glycoprotein...
An unprecedented outbreak of a highly pathogenic avian influenza virus, H5 clade 2.3.4.4b, was reported in United States dairy cattle during the spring 2024. It has now spread to hundreds herds across multiple states. In humans, antibodies hemagglutinin (HA) protein confer strongest protection against infection. Human herd immunity limits viral but also drives emergence antigenic variants that escape dominant antibody responses. We used store-bought milk profile collective H5N1 response...
The rapid appearance of mutations in circulating human influenza viruses and selection for escape from herd immunity require prediction likely variants an annual updating vaccines. identification antibodies that recognize conserved surfaces on the virus hemagglutinin (HA) has prompted efforts to design immunogens might selectively elicit such antibodies.
Endogenous retroviruses (ERVs), remnants of ancient germline infections, comprise 8% the human genome. The most recently integrated includes ERV-K (HERV-K) where several envelope (env) sequences remain intact. Viral pseudotypes decorated with one those Envs are infectious. Using a recombinant vesicular stomatitis virus encoding HERV-K Env as its sole attachment and fusion protein (VSV-HERVK) we conducted genome-wide haploid genetic screen to interrogate host requirements for infection. This...
The coronavirus disease 2019 (COVID-19) pandemic has brought about the unprecedented expansion of highly sensitive molecular diagnostics as a primary infection control strategy. At same time, many laboratories have shifted focus to severe acute respiratory syndrome 2 (SARS-CoV-2) research and diagnostic development, leading large-scale production SARS-CoV-2 nucleic acids that can interfere with these tests. We identified multiple instances, in independent laboratories, which generated...
Cellular eukaryotic replication initiation helicases are first loaded as head-to-head double hexamers on double-stranded (ds) DNA origins and then initiate S-phase melting during licensed (once per cell cycle) replication. Merkel polyomavirus (MCV) large T (LT) helicase oncoprotein similarly binds melts its own 98-bp origin but replicates multiple times in a single cycle. To examine the actions of this unlicensed viral helicase, we quantitated multimerization MCV LT molecules they assembled...
EnvP(b)1 is an endogenous retroviral envelope gene found in human and other primate genomes. We report sequences genomes consistent with integration event between 40 71 million years ago. Using a highly specific polyclonal antiserum raised against the putative receptor binding domain (RBD) of EnvP(b)1, we detected expression placenta, ovaries, thymus. that proteolytically processed, using cell-cell fusion assays multiple cell lines, demonstrated extant proteins from variety are fusogenic....
SARS-CoV-2 NSP12, the viral RNA-dependent RNA polymerase (RdRp), is required for replication and a therapeutic target to treat COVID-19. To facilitate research on NSP12 protein, we developed rat monoclonal antibody (CM12.1) against N-terminus that can functional studies. Immunoblotting immunofluorescence assay (IFA) confirmed specific detection of protein by this cells overexpressing protein. Although generated from ORF1ab polyprotein, IFA human autopsy COVID-19 lung samples revealed...
Abstract Endogenous retroviruses (ERVs), remnants of ancient germline infections, comprise 8% the human genome. The most recently integrated includes ERV-K (HERV-K) where several envelope ( env ) sequences remain intact. Viral pseudotypes decorated with one those Envs are infectious. Using a recombinant vesicular stomatitis virus encoding HERV-K Env as its sole attachment and fusion protein (VSV-HERVK) we conducted genome-wide haploid genetic screen to interrogate host requirements for...
The SARS-CoV-2 pandemic has brought about the unprecedented expansion of highly sensitive molecular diagnostics as a primary infection control strategy. At same time, many laboratories have shifted focus to research and diagnostic development, leading large-scale production nucleic acids that can interfere with these tests. We identified multiple instances, in independent laboratories, which generated settings are suspected caused researchers test positive for surveillance testing. In some...
Abstract Influenza infection and vaccination impart strain-specific immunity that protects against neither seasonal antigenic variants nor the next pandemic. However, antibodies directed to conserved sites can confer broad protection. Here we identify characterize a class of human engage previously undescribed, epitope on influenza hemagglutinin (HA) protein. Prototype antibody S8V1-157 binds at normally occluded interface between HA head stem. Antibodies this head-stem are non-neutralizing...
Abstract Multiple SARS-CoV-2 variants with altered antigenicity have emerged and spread internationally. In one lineage of global concern, we identify a transmitted variant deletion in its receptor binding domain (RBD) that disrupts an epitope which is conserved across sarbecoviruses. Overcoming antigenic variation by selectively focusing immune pressure on this site may, ultimately, drive viral resistance.
ABSTRACT Host genomes have acquired diversity from viruses through the capture of viral elements, often endogenous retroviruses (ERVs). These elements contribute new transcriptional control and protein encoding genes, their refinement evolution can generate novel physiological functions for host. EnvP(b)1 is an retroviral envelope gene found in human other primate genomes. We show that arose very early primates, i.e. at least 40-47 million years ago, but has nevertheless retained its ability...
ABSTRACT Novel animal influenza viruses emerge, initiate pandemics and become endemic seasonal variants that have evolved to escape from prevalent herd immunity. These processes often outpace vaccine-elicited protection. Focusing immune responses on conserved epitopes may impart durable We describe a focused, protective antibody response, abundant in memory serum repertoires, region at the hemagglutinin head interface. Structures of eleven examples, eight reported here, seven human donors...