A5072689092- interferon and immune responses
- Mosquito-borne diseases and control
- Influenza Virus Research Studies
- Immune Response and Inflammation
- Viral Infections and Vectors
- Immune cells in cancer
- Malaria Research and Control
- Immune responses and vaccinations
- Hepatitis C virus research
- Cytokine Signaling Pathways and Interactions
- Inflammasome and immune disorders
- HIV Research and Treatment
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Viral Infections and Immunology Research
- Invertebrate Immune Response Mechanisms
- CAR-T cell therapy research
- NF-κB Signaling Pathways
- Gene expression and cancer classification
- vaccines and immunoinformatics approaches
- RNA modifications and cancer
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Studies on Chitinases and Chitosanases
- Atherosclerosis and Cardiovascular Diseases
Mayo Clinic
2024
University of Washington
2012-2023
Adaptive Biotechnologies (United States)
2022-2023
Alpine Immune Sciences (United States)
2019
Seattle University
2012
University of Arkansas for Medical Sciences
2005-2010
Although the transcription factors IRF-3 and IRF-7 are considered master regulators of type I interferon (IFN) induction IFN stimulated gene (ISG) expression, Irf3−/−×Irf7−/− double knockout (DKO) myeloid dendritic cells (mDC) produce relatively normal levels IFN-β after viral infection. We generated Irf3−/−×Irf5−/−×Irf7−/− triple (TKO) mice to test whether IRF-5 was source residual ISGs in mDCs. In pathogenesis studies with two unrelated positive-sense RNA viruses (West Nile virus (WNV)...
We have used multiplexed high-throughput sequencing to characterize changes in small RNA populations that occur during viral infection animal cells. Small RNA-based mechanisms such as interference (RNAi) been shown plant and invertebrate systems play a key role host responses infection. Although homologs of the RNAi effector pathways are present mammalian cells, can launch an RNAi-mediated degradation experimentally targeted mRNAs, any for host-virus interactions remains be characterized....
Type 1 interferon (IFN) continues to be the foundation for current standard of care combination therapy chronic hepatitis C virus (HCV) infection, yet component interferon-stimulated genes (ISGs) that mediate antiviral actions IFN are not fully defined. Interferon-induced transmembrane protein (IFITM1) is an ISG product suppresses early stage infection by a number viruses through unknown mechanism action. Moreover, IFITM1 on HCV elucidated. Here we identify as hepatocyte tight junction and...
RIG-I pathway signaling of innate immunity against RNA virus infection is organized between the ER and mitochondria on a subdomain called mitochondrial-associated membrane (MAM). The adaptor protein MAVS transmits downstream antiviral immunity, with complexes assembling MAM in association peroxisomes. To identify components that regulate signalosome assembly MAM, we characterized proteome ER, cytosol from cells infected either chronic (hepatitis C) or acute (Sendai) infections, as well...
ABSTRACT The cellular response to virus infection is initiated when pathogen recognition receptors (PRR) engage viral pathogen-associated molecular patterns (PAMPs). This process results in induction of downstream signaling pathways that activate the transcription factor interferon regulatory 3 (IRF3). IRF3 plays a critical role antiviral immunity drive expression innate immune genes, including those encoding factors, type 1 interferon, and modulatory cytokines, act concert restrict...
RIG-I-Like Receptors (RLRs) RIG-I, MDA5, and LGP2, are vital pathogen recognition receptors in the defense against RNA viruses. West Nile Virus (WNV) infections continue to grow US. Here, we use a systems biology approach define contributions of each RLR innate immune response WNV. Genome-wide RNAseq bioinformatics analyses macrophages from mice lacking either reveal that RLRs drive distinct gene activation polarization mediate an M1/inflammatory signature while suppressing M2/wound healing...
ABSTRACT Induction of interferon beta (IFN-β), IFN-stimulated genes (ISGs), and inflammatory responses is critical for control viral infection. We recently identified an essential linkage stimulation the cytokine interleukin-1β (IL-1β) induction ISGs that function as host restriction pathways against emerging flavivirus West Nile virus (WNV) in vivo . Here we utilized ex global transcriptome analysis primary dendritic cells, known targets WNV replication, to define gene signatures required...
Infection with West Nile virus (WNV) leads to a range of disease outcomes, including chronic infection, though lack robust mouse model WNV infection has precluded identification the immune events contributing persistent infection. Using Collaborative Cross, population recombinant inbred strains high levels standing genetic variation, we have identified disease, persistence viral loads within brain. Compared lines exhibiting no or marked F1 cross CC(032x013)F1 displays strong immunoregulatory...
West Nile Virus (WNV), an emerging and re-emerging RNA virus, is the leading source of arboviral encephalitic morbidity mortality in United States. WNV infections are acutely controlled by innate immunity peripheral tissues outside central nervous system (CNS) but can evade actions interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, death. Recent studies indicate that STimulator INterferon Gene (STING), canonically known for initiating a type I IFN...
Abstract The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b influences host susceptibility flavivirus However, impact of Oas on overall programming and global expression among tissues different genetic backgrounds has not been defined. We examined how acts spleen brain tissue limit West Nile (WNV) disease across a range backgrounds. laboratory founder strains Collaborative Cross (CC) (A/J, C57BL/6J,...
Abstract Retinoic acid–inducible gene I (RIG-I) is essential for activating host cell innate immunity to regulate the immune response against many RNA viruses. We previously identified that a small molecule compound, KIN1148, led activation of IFN regulatory factor 3 (IRF3) and served enhance protection influenza A virus (IAV) A/California/04/2009 infection. have now determined direct binding KIN1148 RIG-I drive expression NF-κB target genes, including specific immunomodulatory cytokines...
Although the transcription factors IRF-3 and IRF-7 are considered master regulators of type I interferon (IFN) induction IFN stimulated gene (ISG) expression, Irf3 2/2 6Irf7 double knockout (DKO) myeloid dendritic cells (mDC) produce relatively normal levels IFN-b after viral infection.We generated 6Irf5 triple (TKO) mice to test whether IRF-5 was source residual ISGs in mDCs.In pathogenesis studies with two unrelated positive-sense RNA viruses (West Nile virus (WNV) murine norovirus), TKO...
Significance IFN-stimulated genes (ISGs) are the antiviral effectors and a key component of intracellular innate immunity. Inefficient induction ISGs is linked to poor disease outcome allows viruses establish persistent infection. Hepatitis C virus (HCV) chronically infects over 200 million people worldwide leading cause advanced liver diseases, such as cirrhosis cancer. In this work, our high-throughput cDNA screening identified novel host factor, tyrosine kinase nonreceptor 1, that...
Abstract We examined the signaling pathways and cell type–specific responses of IFN regulatory factor (IRF) 5, an immune-regulatory transcription factor. show that protein kinases IKKα, IKKβ, IKKε, TANK-binding kinase 1 each confer IRF5 phosphorylation/dimerization, thus extending family activator kinases. Among primary human immune subsets, we found is most abundant in plasmacytoid dendritic cells (pDCs). Flow cytometric imaging revealed specifically activated by endosomal TLR signaling....
TruAB Discovery is an approach that integrates cellular immunology, high-throughput immunosequencing, bioinformatics, and computational biology in order to discover naturally occurring human antibodies for prophylactic or therapeutic use. We adapted our previously described pairSEQ technology pair B cell receptor heavy light chains of SARS-CoV-2 spike protein-binding derived from enriched antigen-specific memory cells bulk antibody-secreting cells. identified approximately 60,000 productive,...
Flaviviruses are hematophagous arthropod-viruses that pose global challenges to human health. Like Zika virus, West Nile Virus (WNV) is a flavivirus for which no approved vaccine exists [1]. The role host genetics play in early detection and response WNV still remains largely unexplained. In order capture the impact of genetic variation on innate immune responses, we studied gene expression following infection using collaborative cross (CC). CC mouse resource composed hundreds independently...
Activated CD4 T cells are a major target of HIV infection. Results from the STEP vaccine trial highlighted potential role for total activated in promoting acquisition. However, influence insert-specific cell responses on acquisition is not known. Here, using data obtained four macaque studies, we show that DNA prime/modified vaccinia Ankara boost induced interferon γ (IFNγ+) [T helper 1 (TH1) cells] rapidly migrate to multiple tissues including colon, cervix, and vaginal mucosa. These...
West Nile Virus (WNV) is a mosquito-transmitted virus from the Flaviviridae family that causes fever in 1 5 infected people. WNV can also become neuro-invasive and cross blood-brain barrier leading to severe neurological symptoms subset of individuals [1]. neuro-invasion believed be influenced by number factors including host genetics. In order explore these effects recapitulate complex immune genetic differences among individuals, we studied gene expression following infection Collaborative...
The recognition of pathogen associated molecular patterns (PAMPs) by pattern receptors (PRR) during viral infection initiates the induction antiviral signaling pathways, including activation Interferon Regulator Factor 3 (IRF3). We identified small molecule compounds that activate IRF3 through MAVS, thereby inhibiting viruses families Flaviviridae (West Nile virus, dengue virus and hepatitis C virus), Filoviridae (Ebola Orthomyxoviridae (influenza A Arenaviridae (Lassa virus) Paramyxoviridae...
Abstract Retinoic acid inducible gene I (RIG-I) is essential for directing and priming the host immune response against many RNA viruses. A diverse small molecule library was used in a cell-based screening approach to identify drug-like compounds that could target RIG-I signaling pathway induce downstream IRF3 drive innate antiviral immunity. We identified activate discrete subsets of genes. class hydroxyquinoline activation immunity cultured cells decrease viral load infectious virus...