A5030145353- Influenza Virus Research Studies
- Respiratory viral infections research
- Animal Disease Management and Epidemiology
- RNA and protein synthesis mechanisms
- Viral Infections and Vectors
- Viral gastroenteritis research and epidemiology
- Telomeres, Telomerase, and Senescence
- Viral Infections and Outbreaks Research
- interferon and immune responses
- RNA regulation and disease
- Virus-based gene therapy research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Bacteriophages and microbial interactions
- Muscle Physiology and Disorders
- Infection Control and Ventilation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chromosomal and Genetic Variations
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Chronic Myeloid Leukemia Treatments
Emory University
2008-2024
University of Minnesota
2012
Twin Cities Orthopedics
2012
The 2009 H1N1 lineage represented the first detection of a novel, highly transmissible influenza A virus genotype: six gene segments originated from North American triple-reassortant swine lineage, and two segments, NA M, derived Eurasian avian-like lineage. As neither parental transmits efficiently between humans, adaptations mechanisms underlying pandemic spread swine-origin strain are not clear. To help identify determinants transmission, we used reverse genetics to introduce an early...
ABSTRACT Reassortment of gene segments between coinfecting influenza A viruses (IAVs) facilitates viral diversification and has a significant epidemiological impact on seasonal pandemic influenza. Since 1977, human IAVs H1N1 H3N2 subtypes have cocirculated with relatively few documented cases reassortment. We evaluated the potential for 2009 (pH1N1) lineages to reassort under experimental conditions. Results heterologous coinfections pH1N1 were compared those obtained following coinfection...
The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify that may pose a human public health risk. Since 1999, canine H3 viruses (CIVs) have caused many thousands or millions respiratory infections in dogs United States. While no with CIVs been reported date, these could zoonotic In studies, National Institutes Allergy Infectious Diseases (NIAID) Centers Excellence Influenza Research Surveillance...
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 Position 41 of the influenza A virus matrix protein encodes a highly conserved alanine in human and avian lineages. Nonetheless, strains Eurasian avian-like swine (Easw) lineage contain change at this position: position A/swine/Spain/53207/04 (H1N1) (SPN04) proline. To assess impact naturally occurring polymorphism on viral fitness, we utilized reverse genetics to produce recombinant viruses encoding wild-type M1 41P (rSPN04-P) consensus 41A (rSPN04-A) residues. Relative rSPN04-A,...
2'-5'-Oligoadenylate synthetases (OAS) are innate immune sensors of cytosolic double-stranded RNA (dsRNA) and play a critical role in limiting viral infection. dsRNA binding induces allosteric structural changes OAS1 that reorganize its catalytic center to promote synthesis 2'-5'-oligoadenylate thus activation endoribonuclease L. Specific sequences motifs can also enhance through currently undefined mechanisms. To better understand these drivers OAS activation, we tested the impact defined...
Arenaviruses can cause severe hemorrhagic fever diseases in humans, with limited prophylactic or therapeutic measures. A small RING-domain viral protein Z has been shown to mediate the formation of virus-like particles and inhibit RNA synthesis, although its biological roles an infectious life cycle have not directly addressed. By taking advantage available reverse genetics system for a model arenavirus, Pichinde virus (PICV), we provide direct evidence essential protein's conserved...
The M segment of the 2009 pandemic influenza A virus (IAV) has been implicated in its emergence into human populations. To elucidate genetic contributions to host adaptation, and underlying mechanisms, we examined a panel isogenic viruses that carry avian- or human-derived segments. Avian, but not human, segments restricted viral growth transmission mammalian model systems, correlated with increased expression M2 relative M1. overexpression was associated intracellular accumulation...
Efforts to estimate the risk posed by potentially pandemic influenza A viruses (IAV), and understand mechanisms governing interspecies transmission, have been hampered a lack of animal models that yield relevant statistically robust measures viral fitness. To address this gap, we monitored several quantitative fitness in guinea pig model: infectivity, magnitude replication, kinetics efficiency transmission. With goal identifying metrics distinguish human- non-human-adapted IAV compared...
Abstract One potential advantage of live attenuated influenza vaccines (LAIVs) is their ability to establish both virus-specific Ab and tissue-resident memory T cells (TRM) in the respiratory mucosa. However, it hypothesized that pre-existing immunity from past infections and/or immunizations prevents LAIV boosting or generating de novo CD8+ cell responses. To determine whether we can overcome this limitation, generated a series drifted A/PR8 LAIVs with successive mutations hemagglutinin...
ABSTRACT Establishing effective mitigation strategies to reduce the spread of influenza virus requires an improved understanding mechanisms transmission. We evaluated use a controlled human infection model using H3N2 seasonal study critical aspects transmission, including symptom progression and dynamics shedding. Eight volunteers were challenged with A/Perth/16/2009 (H3N2) between July September 2022 at Emory University Hospital. Viral shedding in nasopharynx, saliva, stool, urine,...
Telomerase is the cellular RNA-dependent DNA polymerase (i.e. reverse transcriptase) that uses an integral RNA template to synthesize telomeric repeats at ends of linear chromosomes. Human telomerase (hTERC) thought function as a dimeric complex consisting two RNAs interact with each other physically well genetically. We show here for first time yeast Saccharomyces cerevisiae TLC1 likewise forms dimers in vitro. dimerization depends on unique 6-base self-complementary sequence, which closely...
Influenza A viral polymerase is a heterotrimeric complex that consists of PA, PB1, and PB2 subunits. We previously reported di-codon substitution mutation (G507A-R508A), denoted J10, in the C-terminal half PA had no apparent effect on RNA synthesis but prevented infectious virus production, indicating may have novel role independent its activity. To further examine roles life cycle, we now generated characterized additional mutations regions flanking J10 site from residues 497 to 518. All...
Abstract The M segment of the 2009 pandemic influenza A virus (IAV) has been implicated in its emergence into human populations. To elucidate genetic contributions to host adaptation, and underlying mechanisms, we examined a panel isogenic viruses that carry avian- or human-derived segments. Avian, but not human, segments restricted viral growth transmission mammalian model systems, correlated with increased expression M2 relative M1. overexpression was associated intracellular accumulation...
The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify that may pose a human public health risk. Since 1999, canine H3 viruses (CIVs) have caused many thousands or millions respiratory infections in dogs United States. While no with CIVs been reported date, these could zoonotic In studies, National Institutes Allergy Infectious Diseases (NIAID) Centers Excellence Influenza Research Surveillance...
Abstract Live attenuated influenza vaccine (LAIV) elicits both humoral and cellular immune memory in children, but its efficacy is limited adults. We hypothesize that pre-existing immunity from past infections and/or immunizations prevents the establishing an response. To determine if we can overcome this limitation by increasing antigenic distance of strain previous circulating seasonal strains, generated a series drifted LAIVs with successive mutations HA protein, allowing for levels...