- Influenza Virus Research Studies
- Respiratory viral infections research
- Immune Response and Inflammation
- interferon and immune responses
- Animal Disease Management and Epidemiology
- Viral Infections and Vectors
- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- RNA modifications and cancer
- Viral Infections and Outbreaks Research
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- Mosquito-borne diseases and control
- Viral Infections and Immunology Research
- Reproductive Physiology in Livestock
- Long-Term Effects of COVID-19
- COVID-19 Clinical Research Studies
- Bacteriophages and microbial interactions
- Hypothalamic control of reproductive hormones
- COVID-19 epidemiological studies
- Protein Structure and Dynamics
- Neuroscience of respiration and sleep
- Eicosanoids and Hypertension Pharmacology
- Estrogen and related hormone effects
National Institute of Allergy and Infectious Diseases
2016-2025
National Institutes of Health
2016-2025
Office of Extramural Research
2019
University of Washington
2002-2007
Seattle University
2006
University of Michigan
1998-2002
Influenza's Cryptic Constraint Because of the well-known pandemic potential influenza viruses, it is important to understand range molecular interactions between virus and its host. Despite years intensive research on virus, Jagger et al. (p. 199 , published online 28 June; see Perspective by Yewdell Ince ) have found that A has been hiding a gene in small negative-sense RNA genome. An overlapping open reading frame was contained PA viral polymerase gene, which accessed ribosomal...
Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from mRNAs 3 and 4 have not previously been identified. The plays important roles in entry assembly, is a target for antiviral drugs vaccination. Surprisingly, essential replication laboratory setting, although its loss attenuates virus. To better understand how IAV might replicate without M2, we studied reversion mechanism an M2-null...
Lung epithelial and endothelial cell damage defective lung tissue repair contribute to fatal COVID-19.
We studied the effect of filovirus infection on host cell gene expression by characterizing regulation responses in human liver cells infected with Zaire Ebolavirus (ZEBOV), Reston (REBOV), and Marburgvirus (MARV), using transcriptional profiling bioinformatics. Expression microarray analysis demonstrated that resulted up-regulation immune-related genes down-regulation many coagulation acute-phase proteins. These studies further revealed a common feature virulence is suppression key cellular...
The 1918 to 1919 “Spanish” influenza pandemic virus killed up 50 million people. We report here clinical, pathological, bacteriological, and virological findings in 68 fatal American influenza/pneumonia military patients dying between May October of 1918, a period that includes ∼4 mo before the was recognized, 2 (September–October 1918) during which it appeared peaked. lung tissues 37 these cases were positive for viral antigens or RNA, including four from prepandemic (May–August). peak...
ABSTRACT Secondary bacterial infections increase disease severity of influenza virus and contribute greatly to increased morbidity mortality during pandemics. To study secondary infection following infection, mice were inoculated with sublethal doses 2009 seasonal H1N1 (NIH50) or pandemic (Mex09) followed by inoculation Streptococcus pneumoniae 48 h later. Disease was characterized assessment weight loss survival, titration bacteria quantitative reverse transcription-PCR (qRT-PCR),...
The devastating potential of influenza has been well known for over 100 years. Despite the development vaccines since middle 20th century, continues to be responsible substantial global morbidity and mortality. To develop next-generation with enhanced effectiveness, we must synthesize our understanding complex immune mechanisms culminating in protection. Our study outlines differences responses vaccine infection, identifying gaps vaccine-induced immunity, particularly at level nasal mucosa....
Viral infections of the central nervous system (CNS) are a major cause morbidity largely due to lack prevention and inadequate treatments. While mortality from viral CNS is significant, nearly two thirds patients survive. Thus, it important understand how human can successfully control virus infection recover. Since not possible study throughout course at cellular level, here we analyzed non-lethal in nonhuman primates (NHPs). We inoculated NHPs intracerebrally with high dose La Crosse...
To understand more fully the molecular events associated with highly virulent or attenuated influenza virus infections, we have studied effects of expression 1918 hemagglutinin (HA) and neuraminidase (NA) genes during viral infection in mice under biosafety level 3 (agricultural) conditions. Using histopathology cDNA microarrays, examined consequences HA NA pandemic a recombinant A/WSN/33 compared to parental an expressing from A/New Caledonia/20/99. The HA/NA:WSN WSN viruses were lethal for...
Influenza virus infections are a global public health problem, with significant impact of morbidity and mortality from both annual epidemics pandemics. The current strategy for preventing influenza is to develop new vaccine each year against specific circulating strains. Because these vaccines unlikely protect an antigenically divergent strain or pandemic novel hemagglutinin (HA) subtype, there critical need that all A viruses, so-called "universal" vaccine. Here we show mice were broadly...
Please cite this paper as: Easterbrook et al. (2011) Obese mice have increased morbidity and mortality compared to non-obese during infection with the 2009 pandemic H1N1 influenza virus. Influenza Other Respiratory Viruses 5(6), 418–425. Background Obesity has been identified as an independent risk factor for severe or fatal (2009 pH1N1), but was not previously recognized previous seasonal infections. Objectives Our aim evaluate role of obesity severity pH1N1, H1N1, a pathogenic Methods...
The 1918 influenza pandemic caused more than 40 million deaths and likely resulted from the introduction adaptation of a novel avian-like virus. Influenza A virus hemagglutinins are important in host switching virulence. Avian-adapted bind sialic acid receptors linked via alpha2-3 glycosidic bonds, while human-adapted alpha2-6 receptors. Sequence analysis isolates showed hemagglutinin genes with or mixed alpha2-6/alpha2-3 binding. To characterize role binding specificity hemagglutinin, we...
Most biopsy and autopsy tissues are formalin-fixed paraffin-embedded (FFPE), but this process leads to RNA degradation that limits gene expression analysis. The genome of the 1918 pandemic influenza virus was previously determined in a 9-year effort by overlapping RT-PCR from post-mortem samples. Here, full at 3000× coverage one high-throughput sequencing run library derived total FFPE sample after duplex-specific nuclease treatments. Bacterial sequences associated with secondary bacterial...
Identification of correlates protection against human influenza A virus infection is important in development broadly protective ("universal") vaccines. Certain assumptions underlie current vaccine developmental strategies, including that with a particular should offer long-term or lifelong strain, preventing reinfection. In this study we report observations made when 7 volunteers participated sequential challenge studies where they were challenged intranasally using the identical...
Abstract Background Preclinical animal studies and retrospective human suggest that adult females have worse outcomes from influenza than males. Prospective in humans are missing. Methods Data 164 healthy volunteers who underwent A/California/04/2009/H1N1 challenge were compiled to compare differences between sexes. Baseline characteristics, including hormone levels, hemagglutination inhibition (HAI) titers, neuraminidase (NAI) after compared. Linear logistic regression models built...
Cells have evolved elaborate mechanisms to counteract the onslaught of viral infections. To activate these defenses, threat must be recognized. Danger signals, or pathogen-associated molecular patterns, that are induced by pathogens include double-stranded RNA (dsRNA), single-stranded RNA, glycolipids, and CpG DNA. Understanding signal transduction pathways activated host gene expression danger signals is vital understanding virus-host interactions. The vaccinia virus E3L protein involved in...
The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first pandemic 41 years. has spread efficiently to both Northern Southern Hemispheres been associated with over 16,000 deaths. Given virus's recent zoonotic origin, there is concern that could acquire signature mutations enhanced pathogenicity of previous viruses or H5N1 potential. We tested hypothesis polymerase PB2 gene at residues 627 701 would enhance virulence but found containing these context complex are...