A5101563016- Influenza Virus Research Studies
- Respiratory viral infections research
- Rabbits: Nutrition, Reproduction, Health
- Animal Behavior and Welfare Studies
- Primate Behavior and Ecology
- Viral Infections and Immunology Research
- Immune Response and Inflammation
- Viral gastroenteritis research and epidemiology
- Metabolism and Genetic Disorders
- interferon and immune responses
- Mitochondrial Function and Pathology
- Immune Cell Function and Interaction
- Gut microbiota and health
- Neonatal Respiratory Health Research
- Viral Infections and Vectors
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Viral Infections and Outbreaks Research
- ATP Synthase and ATPases Research
- Protein Degradation and Inhibitors
- Animal Disease Management and Epidemiology
- Advanced Glycation End Products research
- Epigenetics and DNA Methylation
- Shoulder Injury and Treatment
- Steroid Chemistry and Biochemistry
Manubhai Patel Dental College and Hospital
2024
Commonwealth Medical College
2023
Centers for Disease Control and Prevention
2019-2023
L'Oreal (United States)
2023
Institute of Genomics and Integrative Biology
2023
Harvard University
2023
Pondicherry University
2023
National Center for Immunization and Respiratory Diseases
2019-2023
Vanderbilt University
2022-2023
Center for Surveillance, Epidemiology, and Laboratory Services
2022
RNA polymerase II (Pol II) and the pausing complex, NELF DSIF, are detected near transcription start site (TSS) of many active silent genes. Active starts when pause release factor P-TEFb is recruited to initiate productive elongation. However, mechanism recruitment regulation NELF/DSIF during not fully understood. We investigated this question in interferon (IFN)-stimulated transcription, focusing on BRD4, a BET family protein that interacts with P-TEFb. Besides P-TEFb, BRD4 binds...
Epigenetic memory for signal-dependent transcription has remained elusive. So far, the concept of epigenetic been largely limited to cell-autonomous, preprogrammed processes such as development and metabolism. Here we show that IFNβ stimulation creates transcriptional in fibroblasts, conferring faster greater upon restimulation. The was inherited through multiple cell divisions led improved antiviral protection. Of ∼2,000 IFNβ-stimulated genes (ISGs), about half exhibited memory, which...
Abstract Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, viral infections, influenza infection. Thus, therapeutic control of the TLR4 signalling pathway major interest. Here we tested activity small-molecule synthetic antagonist, FP7, vitro on human monocytes monocyte-derived dendritic cells (DCs) vivo during virus infection mice. Our results indicate that FP7 antagonized secretion...
The anti-influenza therapeutic baloxavir targets cap-dependent endonuclease activity of polymerase acidic (PA) protein. We monitored susceptibility in the United States with next generation sequencing analysis supplemented by phenotypic one-cycle infection assay. Analysis PA sequences 6,891 influenza A and B viruses collected during 2016/17 2017/18 seasons showed amino acid substitutions: I38L (two A(H1N1)pdm09 viruses), E23G viruses) I38M (one A(H3N2) virus); conferring 4-10-fold reduced to...
Toll-like receptors (TLRs) are sentinel of the host innate immune system that recognize conserved 'pathogen-associated molecular patterns' invading microbes, including viruses. The activation TLRs establishes antiviral responses and coordinates development long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage tissues may release 'danger-associated also activate TLRs, leading an overexuberant inflammatory response and, ultimately, tissue...
Baloxavir showed broad-spectrum in vitro replication inhibition of 4 types influenza viruses (90% effective concentration range 1.2-98.3 nmol/L); susceptibility pattern was A ˃ B C D. This drug also inhibited avian and swine origin, including that have pandemic potential those resistant to neuraminidase inhibitors.
ABSTRACT Mitochondria and peroxisomes are dynamic signaling organelles that constantly undergo fission, driven by the large GTPase dynamin-related protein 1 (DRP1; encoded DNM1L). Patients with de novo heterozygous missense mutations in DNM1L present encephalopathy due to defective mitochondrial peroxisomal fission (EMPF1) – a devastating neurodevelopmental disease no effective treatment. To interrogate mechanisms which DRP1 cause cellular dysfunction, we used human-derived fibroblasts from...
We describe the complete synthesis, assembly, debugging, and characterization of a synthetic 404,963 bp chromosome,
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Maternal immunization an option to increase maternal antibody levels and protect infants from infection. Here we assess efficacy virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations RSV F protein attachment G a model using cotton rats. VLP vaccines proteins strongly boost pre-existing immunity dams preventing their perinatal drop...
ABSTRACT Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression severity for inflammatory infectious diseases. There is accumulating evidence that generation DAMPs such oxidized phospholipids high-mobility-group box 1 (HMGB1) during influenza virus infection leads acute lung injury (ALI). Treatment virus-infected mice cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP...
Since May 2023, a novel combination of neuraminidase mutations, I223V + S247N, has been detected in influenza A(H1N1)pdm09 viruses collected countries spanning 5 continents, mostly Europe (67/101). The belong to 2 phylogenetically distinct groups and display ≈13-fold reduced inhibition by oseltamivir while retaining normal susceptibility other antiviral drugs.
Monkeypox, a zoonotic viral disease, has re-emerged globally, presenting significant public health challenge. Initially affecting primarily men who have sex with men, the virus demonstrated broader transmission patterns, raising concerns about its potential to become endemic. The recent outbreak highlighted rapid spread of Monkeypox through close contact, particularly during sexual activity. This shift in dynamics necessitates robust global response, including surveillance systems, contact...
In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68) among patients with severe respiratory infections worldwide. EV-D68 is now recognized as re-emerging pathogen; however, due to lack permissive animal model for EV-D68, comprehensive understanding the pathogenesis and immune response against hampered. Recently, it was shown that strong affinity α2,6-linked sialic acids (SAs) we have previously SAs are abundantly present tract cotton rats (Sigmodon...
Susceptibility of influenza A viruses to baloxavir can be affected by changes at amino acid residue 38 in the polymerase acidic (PA) protein. Information on replicative fitness PA-I38-substituted remains sparse. We demonstrated that substitutions I38L/M/S/T not only had a differential effect susceptibility (9- 116-fold) but also vitro fitness. Although I38L conferred undiminished growth, other led mild attenuation. In ferret model, control outcompeted those carrying I38M or I38T...
Pimodivir exerts an antiviral effect on the early stages of influenza A virus replication by inhibiting cap-binding function polymerase basic protein 2 (PB2). In this study, we used a combination sequence analysis and phenotypic methods to evaluate pimodivir susceptibility viruses collected from humans other hosts. Screening PB2 sequences for substitutions previously associated with reduced revealed very low frequency among seasonal circulating in U.S. during 2015–2020 (<0.03%; 3/11,934)...
In HIV-1 infection, plasmacytoid dendritic cell (PDC) numbers and function are decreased. No detailed comparisons of PDC responses to various stimuli in HIV-1-infected patients available. Using for the first time purified PDCs, we compared [interferon (IFN)-α production/cell] a large number (n=48) healthy volunteers (n=19). Toll-like receptor (TLR)7- TLR9-induced expression surface activation maturation markers was also two populations. We have confirmed that coincides with CD4(+) T counts...
Baloxavir, a new antiviral drug targeting cap-dependent endonuclease activity of polymerase acidic (PA) protein influenza viruses, is now approved in multiple countries. Several substitutions at isoleucine 38 PA (e.g., PA-I38T) have been associated with decreased baloxavir susceptibility vitro and vivo. In recent years, next generation sequencing (NGS) analysis pyrosequencing used by CDC U.S. Public Health Laboratories to monitor viruses. Here we described an improved assay for detecting A...
Abstract Background Understanding respiratory syncytial virus (RSV) global epidemiology is important to inform future prevention strategies. Methods Hospitalized infants &lt;1-year-old with acute illness were enrolled prospectively in Albania, Jordan, Nicaragua, and Philippines during seasons 2015–2017. Medical chart review, parental interview, post-discharge follow up conducted. Respiratory specimens tested using real-time RT-PCR for RSV. Infant characteristics associated very severe...