A5028275209- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Facial Rejuvenation and Surgery Techniques
- Viral gastroenteritis research and epidemiology
- COVID-19 Pandemic Impacts
- Head and Neck Surgical Oncology
- Facial Nerve Paralysis Treatment and Research
- Reconstructive Facial Surgery Techniques
- Body Image and Dysmorphia Studies
- Nasal Surgery and Airway Studies
- Sinusitis and nasal conditions
- Influenza Virus Research Studies
- RNA regulation and disease
- Digital Imaging in Medicine
- Salivary Gland Tumors Diagnosis and Treatment
- CRISPR and Genetic Engineering
- COVID-19 Clinical Research Studies
- Plant Virus Research Studies
- interferon and immune responses
- Viral Infections and Immunology Research
- Poxvirus research and outbreaks
- Orthopedic Surgery and Rehabilitation
- Peripheral Nerve Disorders
- Laser Applications in Dentistry and Medicine
- Cleft Lip and Palate Research
University of Utah
2020-2025
Howard Hughes Medical Institute
2022-2025
MedStar Washington Hospital Center
2001-2020
Dignity Health
2020
University of Pennsylvania
2005-2019
University of Arizona
2011-2016
NYU Langone Health
2012
Harvard University
2012
Massachusetts Eye and Ear Infirmary
2012
Philadelphia University
1999-2004
Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing future zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market Wuhan, China, was identified as a likely source of cases early reports, but later this conclusion became controversial. We show here that earliest known COVID-19 from December 2019, including those without reported direct links, were geographically centered on market. report...
Significance RNase L, an antiviral enzyme activated during infection, degrades viral and cellular RNAs, inhibits protein synthesis, restricts the replication spread of diverse viruses. L activation depends on 2′,5′-oligoadenylates synthesized by different oligoadenylate synthetases (OASs), i.e., OAS1, OAS2, OAS3. OASs are induced interferon dsRNA. It has been unclear which these OAS proteins is necessary and/or sufficient to activate infections. We show that OAS3, but not OAS1 or required...
ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. Mutation of leads to a severe neurodevelopmental inflammatory disease children, Aicardi-Goutiéres syndrome. In mice, Adar1 mutations embryonic lethal but rescued by mutation the Mda5 or Mavs genes, which function in IFN induction. However, specific regulated proteins responsible for pathogenic effects unknown. We show cell-lethal phenotype deletion human lung...
Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human to emerge since severe acute (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins are not required for replication of genome but likely involved pathogenesis. Evasion host innate immunity through interferon (IFN) antagonism a critical component viral The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing...
Middle East respiratory syndrome coronavirus (MERS-CoV) is the second novel zoonotic to emerge in 21st century and cause outbreaks of severe disease. More than 2,200 cases 800 deaths have been reported date, yet there are no licensed vaccines or treatments. Coronaviruses encode unique accessory proteins that not required for replication but most likely play roles immune antagonism and/or pathogenesis. Our study describes functions MERS-CoV NS4a NS4b during infection a human airway-derived...
Phosphodiesterases (PDEs) encoded by viruses are putatively acquired horizontal transfer of cellular PDE ancestor genes. Viral PDEs inhibit the OAS-RNase L antiviral pathway, a key effector component innate immune response. Although function these proteins is well-characterized, origins gene acquisitions less clear. Phylogenetic analysis revealed at least five independent acquisition events ancestral viruses. We found evidence that PDE-encoding genes were horizontally transferred between...
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...
The ongoing SARS-CoV-2 pandemic is the third zoonotic coronavirus identified in last 20 years. Enzootic and epizootic coronaviruses of diverse lineages also pose a significant threat to livestock, as most recently observed for virulent strains porcine epidemic diarrhea virus (PEDV) swine acute diarrhea-associated (SADS-CoV). Unique RNA viruses, encode proofreading exonuclease (ExoN) that lowers point mutation rates increase viability large genomes, which comes with cost limiting adaptation...
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.
Horizontal gene transfer (HGT) provides a major source of genetic variation. Many viruses, including poxviruses, encode genes with crucial functions directly gained by from hosts. The mechanism to poxvirus genomes is unknown. Using genome analysis and experimental screens infected cells, we discovered central role for Long Interspersed Nuclear Element-1 retrotransposition in HGT virus genomes. process recapitulates processed pseudogene generation, but host messenger RNA directed into...
Understanding the genomic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at outset disease 2019 pandemic can provide insight into circumstances leading to its emergence. Early SARS-CoV-2 has been classified two distinct viral lineages, denoted "A" and "B," which we hypothesized were separately introduced humans. Recently published data contain genomes with a haplotype suggested be an evolutionary intermediate these known as "T/T." We used phylodynamic approach...
The ongoing SARS-CoV-2 pandemic is the third zoonotic coronavirus identified in last twenty years. Enzootic and epizootic coronaviruses of diverse lineages also pose a significant threat to livestock, as most recently observed for virulent strains porcine epidemic diarrhea virus (PEDV) swine acute diarrhea-associated (SADS-CoV). Unique RNA viruses, encode proofreading exonuclease (ExoN) that lowers point mutation rates increase viability large genomes, which comes with cost limiting...
Acyclovir-resistant herpes simplex virus (HSV) has become increasingly common, particularly among patients with human immunodeficiency (HIV).We present a case of acyclovir-resistant HSV treated intralesional cidofovir. REPORT OF A CASEA 34-year-old HIV-positive man known history recurrent genital infection presented an exophytic, left-sided nasal lesion ulceration.Multiple biopsy specimens only showed extensive granulation tissue, and indurated, ulcerated plaque recurred progressed despite...
ABSTRACT Viruses in the family Coronaviridae , within order Nidovirales are etiologic agents of a range human and animal diseases, including both mild severe respiratory diseases humans. These viruses encode conserved replicase structural proteins as well more diverse accessory proteins, encoded 3′ ends their genomes, that often act host cell antagonists. We previously showed 2′,5′-phosphodiesterases (2′,5′-PDEs) by prototypical Betacoronavirus mouse hepatitis virus (MHV), Middle East...
Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse offers platform studying acute transmission of between within hosts via mechanisms. We identified numerous other microbial species that transmit to mice, including prospective new...
Zoonotic spillovers of viruses have occurred through the animal trade worldwide. The start COVID-19 pandemic was traced epidemiologically to Huanan Wholesale Seafood Market, site with most reported wildlife vendors in city Wuhan, China. Here, we analyze publicly available qPCR and sequencing data from environmental samples collected market early 2020. We demonstrate that SARS-CoV-2 genetic diversity linked this is consistent emergence, find increased positivity near within a particular...