A5021234627- Influenza Virus Research Studies
- Respiratory viral infections research
- Animal Disease Management and Epidemiology
- Immune Response and Inflammation
- interferon and immune responses
- Bacteriophages and microbial interactions
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Herpesvirus Infections and Treatments
- Plant Virus Research Studies
- Plant and Fungal Interactions Research
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Trypanosoma species research and implications
- RNA Interference and Gene Delivery
- Receptor Mechanisms and Signaling
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- COVID-19 epidemiological studies
- Microbial infections and disease research
- RNA regulation and disease
- Cytomegalovirus and herpesvirus research
- Lysosomal Storage Disorders Research
Pfizer (United States)
2022-2025
Icahn School of Medicine at Mount Sinai
2005-2022
Rutgers, The State University of New Jersey
2014-2017
Virginia–Maryland College of Veterinary Medicine
2008-2010
University of Maryland, College Park
2007-2010
National Center for Infectious Diseases
2005-2007
Centers for Disease Control and Prevention
2005-2007
U.S. National Poultry Research Center
2005-2007
Armed Forces Institute of Pathology
2005
St. Jude Children's Research Hospital
2005
The pandemic influenza virus of 1918-1919 killed an estimated 20 to 50 million people worldwide. With the recent availability complete 1918 coding sequence, we used reverse genetics generate bearing all eight gene segments study properties associated with its extraordinary virulence. In stark contrast contemporary human H1N1 viruses, had ability replicate in absence trypsin, caused death mice and embryonated chicken eggs, displayed a high-growth phenotype bronchial epithelial cells....
The 1918 influenza pandemic was a catastrophic series of virus outbreaks that spread across the globe. Here, we show only modest change in hemagglutinin receptor binding site alters transmissibility this virus. Two amino acid mutations cause switch preference from human α-2,6 to avian α-2,3 sialic resulted incapable respiratory droplet transmission between ferrets but maintained its lethality and replication efficiency upper tract. Furthermore, poor with dual specificity suggests predominant...
The Spanish influenza pandemic of 1918 to 1919 swept the globe and resulted in deaths at least 20 million people. basis pulmonary damage high lethality caused by H1N1 virus remains largely unknown. Recombinant viruses bearing hemagglutinin (HA) neuraminidase (NA) glycoproteins were rescued genetic background human A/Texas/36/91 (H1N1) (1918 HA/NA:Tx/91) virus. Pathogenesis experiments revealed that HA/NA:Tx/91 was lethal for BALB/c mice without prior adaptation is usually required A viruses....
Abstract Therapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability inefficient protein expression. Here, we describe design principles that overcome these barriers. We develop an RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell stability, ribosome load, as well in-solution stability library diverse mRNAs. find that, surprisingly, greater driver...
Due to the high mortality associated with recent, widely circulating strains of H5N1 influenza virus in poultry, recurring introduction viruses from birds humans, and difficulties eradication by elimination affected flocks, an effective vaccine against HPAI (highly pathogenic avian influenza) is highly desirable. Using reverse genetics, a set experimental live attenuated based on recombinant A/Viet Nam/1203/04 was generated. Each through expression hemagglutinin protein which polybasic...
It has been shown previously that the nonstructural protein NS1 of influenza virus is an alpha/beta interferon (IFN-alpha/beta) antagonist, both in vitro and experimental animal model systems. However, evidence this function a natural host not yet obtained. Here we investigated role virulence swine (SIV) isolate pigs by using reverse genetics. The virulent wild-type A/Swine/Texas/4199-2/98 (TX/98) various mutants encoding carboxy-truncated proteins were rescued. Growth properties TX/98...
The IFN-induced resistance factor Mx1 is a critical component of innate immunity against influenza A viruses (FLUAV) in mice. Animals carrying wild-type gene (Mx1(+/+)) differ from regular laboratory mice (Mx1(-/-)) that they are highly resistant to infection with standard FLUAV strains. We identified an extraordinary variant the strain, A/PR/8/34 (H1N1) (designated hvPR8), which unusually virulent Mx1(+/+) hvPR8 was well controlled but not Mx1(-/-) provided animals were treated IFN before...
ABSTRACT Swine influenza viruses (SIV) naturally infect pigs and can be transmitted to humans. In the pig, genetic reassortment create novel subtypes by mixing avian, human, swine is possible. An SIV vaccine inducing cross-protective immunity between different strains circulating in highly desirable. Previously, we have shown that an H3N2 (A/swine/Texas/4199-2/98 [TX98]) containing a deleted NS1 gene expressing truncated protein of 126 amino acids, NS1▴126, was attenuated swine. this study,...
Without baseline human immunity to the emergent avian influenza A(H7N9) virus, neuraminidase inhibitors are vital for controlling viral replication in severe infections. An amino acid change associated with drug resistance, NA-R292K (N2 numbering), has been found some H7N9 clinical isolates. Here we assess impact of substitution on antiviral sensitivity and replication, pathogenicity transmissibility viruses. Our data indicate that an isolate encoding is highly resistant oseltamivir...
The 1918 influenza pandemic was exceptionally severe, resulting in the death of up to 50 million people worldwide. Here, we show which virus genes contributed replication and virulence virus. Recombinant viruses, were replaced with from a contemporary human H1N1 virus, A/Texas/36/91 (Tx/91), generated. exchange most seasonal did not alter virus; however, substitution hemagglutinin (HA), neuraminidase (NA), or polymerase subunit PB1 significantly affected ability this cause severe disease...
Influenza viruses evade human adaptive immune responses due to continuing antigenic changes. This makes it necessary re-formulate and re-administer current seasonal influenza vaccines on an annual basis. Our pan-influenza vaccination approach attempts redirect antibody from the variable, immuno-dominant hemagglutinin head towards conserved-but immuno-subdominant-hemagglutinin stalk. The strategy utilizes sequential immunization with chimeric hemagglutinin-based expressing exotic domains, a...
BackgroundInfluenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can considerable mismatches between vaccine strains, substantially reducing effectiveness. Moreover, current seasonal are ineffective pandemic influenza, production of a newly emerging virus strain takes months. Therefore, there is an unmet medical need for broadly protective vaccine. We...
Effective antibody responses provide crucial immunity against influenza virus infection. The hemagglutinin (HA) protein is the major target of protective induced by viral infection and vaccination with both inactivated live-attenuated flu vaccines, but knowledge about optimal designs HA antigens from different serotypes still limited. In this study, we have significantly improved immunogenicity HA-expressing DNA vaccines using codon-optimized sequences for either an H1 serotype...
ABSTRACT We are still inadequately prepared for an influenza pandemic due to the lack of a vaccine effective subtypes which majority human population has no prior immunity and could be produced rapidly in sufficient quantities. There is therefore urgent need investigate novel vaccination approaches. Using combination genomic traditional tools, this study compares protective efficacy macaques intrarespiratory live virus by truncating NS1 A/Texas/36/91 (H1N1) with that conventional based on...
Due to continuous antigenic drift and occasional shift, influenza viruses escape from human adaptive immunity resulting in significant morbidity mortality humans. Therefore, avoid the need for annual reformulation readministration of seasonal virus vaccines, we are developing a novel chimeric hemagglutinin (cHA)-based universal vaccine, which is comprised sequential immunization with antigens containing conserved stalk domain derived circulating pandemic H1N1 strain combination "exotic" head...
Triple-reassortant swine influenza viruses circulating in North American pigs contain the internal genes derived from (matrix, non-structural and nucleoprotein), human [polymerase basic 1 (PB1)] avian (polymerase acidic PB2) forming a constellation of that is well conserved called triple-reassortant gene (TRIG) cassette. In contrast, external [haemagglutinin (HA) neuraminidase (NA)] are less conserved, reflecting multiple reassortant events have produced with different combinations HA NA...
Influenza pandemics occur when influenza A viruses (IAV) adapted to other host species enter humans and spread through the population. Pandemics are relatively rare due restriction of IAV: strains nonhuman do not readily infect, replicate in, or transmit among humans. IAV can overcome reassortment adaptive evolution, these mechanisms by which pandemic arise in nature. To identify mutations that facilitate growth avian humans, we have A/duck/Alberta/35/1976 (H1N1) (dk/AB/76) virus a...
Abstract Herpes zoster (HZ) is a painful vesicular rash that occurs upon varicella-zoster virus (VZV) reactivation in older adults and immunocompromised individuals. Although there currently an approved vaccine for the prevention of shingles, its administration commonly associated with high reactogenicity. This highlights need to develop new alternatives long lasting immunity improved tolerability administration. In present study, 10 different candidate designs using two codon optimizations...
CLN3 disease is a prevalent form of Neuronal Ceroid Lipofuscinosis (NCL) caused by inherited mutations in the gene, with symptoms such as vision loss, language impairment, and cognitive decline. The early onset visual deficits complicates neurological assessment brain pathophysiology underlying decline, while small number mutation cases humans hinders study sex differences. Building on our recent progress assessing auditory neurophysiological changes patients, we developed parallel approach...
Human influenza is a seasonal disease associated with significant morbidity and mortality. Influenza vaccination the most effective means for prevention. We have previously shown that mutations in PB1 PB2 genes of live-attenuated vaccine (LAIV) from cold-adapted (ca) virus A/Ann Arbor/6/60 (H2N2) could be transferred to avian viruses produce partially attenuated viruses. also demonstrated carrying further by stably introducing hemagglutinin (HA) epitope tag gene. In this work, we wanted...
A naturally occurring lymphoproliferative disease was found in 3 flocks of Japanese quail Mexico. The tumorlike lesions were detected mainly livers and spleens. Histopathology revealed a pleomorphic infiltration with dark-staining large cells, lymphocytes different sizes, reticulumlike cells. Marek's (MD) herpesvirus not isolated from 74 tested, nor antibodies to MD 84 sera. Antibodies reticuloendotheliosis (3/24) avain leukosis virus subgroup (2/24) present. possible etiology this is discussed.
ABSTRACT Avian influenza A viruses have gained increasing attention due to their ability cross the species barrier and cause severe disease in humans other mammal as pigs. H3 particularly H3N8 viruses, are highly adaptive since they found multiple avian hosts. not been isolated yet from humans; however, a recent report showed that equine (IAVs) can be pigs, although an established infection has observed thus far this host. To gain insight into possibility of IAVs vitro experiments...