A5009461787- Influenza Virus Research Studies
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- interferon and immune responses
- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- Viral gastroenteritis research and epidemiology
- Immune Response and Inflammation
- COVID-19 Clinical Research Studies
- RNA Research and Splicing
- Zoonotic diseases and public health
- Viral Infections and Immunology Research
- Mosquito-borne diseases and control
- Animal Virus Infections Studies
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- Respiratory Support and Mechanisms
- SARS-CoV-2 detection and testing
- RNA Interference and Gene Delivery
- Long-Term Effects of COVID-19
- Animal Disease Management and Epidemiology
- Viral Infections and Vectors
- MicroRNA in disease regulation
- Monoclonal and Polyclonal Antibodies Research
University of Minnesota
2016-2025
University of Minnesota System
2019-2025
University of Minnesota Medical Center
2016-2024
Institute of Molecular Biology and Biophysics
2020-2024
Twin Cities Orthopedics
2022
Institute of Immunology
2022
Minot State University
2021
Icahn School of Medicine at Mount Sinai
2011-2016
Applied Research Associates (United States)
2013
University of Iowa
2007-2011
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target receptor binding domain of spike (S) protein, a focus successful vaccine efforts. Concerns have arisen that S-specific immunity may fail to neutralize emerging variants. We show vaccination with human adenovirus type 5 vector expressing SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian...
Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory in providing against syncytial virus (RSV) infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust cell responses absence RSV-specific CD4 antibodies. Unexpectedly, RSV mice with pre-existing led exacerbated weight loss, pulmonary disease, lethal immunopathology. The...
Numerous observations indicate that resident memory T cells (TRM) undergo unusually rapid attrition within the lung. Here we demonstrate contraction of lung CD8+ cell responses after influenza infection is contemporized with egress CD69+/CD103+ to draining mediastinal LN via lymphatic vessels, which term retrograde migration. Cells retained canonical markers TRM, including CD103 and CD69, lacked Ly6C expression (also a feature TRM), maintained granzyme B expression, did not equilibrate among...
Humans differ in their susceptibility to infectious disease, partly owing variation the immune response after infection. We used single-cell RNA sequencing quantify influenza infection peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European associated with increased I interferon pathway activity early infection, which predicts reduced viral titers at later time points....
The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how heterogeneity this diverse population contributes elements viral tropism pathogenesis, antiviral immunity, treatment response remdesivir. found that, while a variety epithelial types are susceptible infection, ciliated cells predominant target SARS-CoV-2. host protease TMPRSS2 was required for infection these cells. Importantly, remdesivir...
The SARS-CoV-2 virus enters cells via Angiotensin-converting enzyme 2 (ACE2), disrupting the renin-angiotensin-aldosterone axis, potentially contributing to lung injury. Treatment with angiotensin receptor blockers (ARBs), such as losartan, may mitigate these effects, though induction of ACE2 could increase viral entry, replication, and worsen disease.
SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates injury in preclinical models, although data humans with remain mixed.To test the efficacy of losartan reduce hospitalized patients COVID-19.This blinded, placebo-controlled randomized clinical trial was conducted 13 hospitals United States from April 2020 February 2021. Hospitalized and a respiratory sequential organ failure assessment...
Dengue virus (DENV) is a mosquito-borne pathogen for which no vaccine or specific therapeutic available. Although it well established that dendritic cells and macrophages are primary sites of DENV replication, remains unclear whether non-hematopoietic cellular compartments serve as reservoirs. Here, we exploited hematopoietic-specific microRNA-142 (miR-142) to control tropism by inserting tandem target into the restrict replication exclusively in this cell population. In vivo use restricted...
microRNAs (miRNAs) represent a class of noncoding RNAs that fine-tune gene expression through post-transcriptional silencing. While miRNA biogenesis occurs in stepwise fashion, initiated by the nuclear microprocessor, rare noncanonical miRNAs have also been identified. Here we characterize molecular components and unique attributes associated with processing virus-derived cytoplasmic primary (c-pri-miRNAs). RNA situ hybridization inhibition cellular division demonstrated complete lack...
Influenza A virus is unique as an RNA in that it replicates the nucleus and undergoes splicing. With only ten major proteins, must gain nuclear access, replicate, assemble progeny virions cytoplasm, then egress. In effort to elucidate coordination of these events, we manipulated transcript levels from bicistronic nonstructural segment encodes spliced product responsible for genomic export. We find utilization erroneous splice site ensures slow accumulation viral export protein (NEP) while...
Respiratory infection of influenza A virus (IAV) is frequently characterized by extensive immunopathology and proinflammatory signaling that can persist after clearance. In this report, we identify cells become infected, but survive, acute infection. We demonstrate these cells, known as club elicit a robust transcriptional response to infection, show increased interferon stimulation, induce high levels cytokines successful viral Specific depletion surviving leads reduction in lung tissue...
A successful cellular response to virus infection is essential for evolutionary survival. In plants, arthropods, and nematodes, antiviral defenses rely on RNAi. Interestingly, the mammalian predominantly orchestrated through interferon (IFN)-mediated induction of proteins. Despite potency IFN system, it remains unclear whether mammals also have capacity employ Here, we investigated this by disabling function, small RNA or both activities in context infection. We find that loss RNAs an vivo...
Virus–host cell interactions initiate a host cell–defensive response during virus infection. How transposable elements in the respond to viral stress at molecular level remains largely unclear. By reanalyzing next generation sequencing data sets from dozens of infection studies Gene Expression Omnibus database, we found that genome-wide transposon expression up-regulation cells occurs near antiviral genes and exists all regardless virus, species, tissue types. Some transposons were be...
Naive CD4+ T lymphocytes differentiate into various Th cell subsets following TCR binding to microbial peptide:MHC class II (p:MHCII) complexes on dendritic cells (DCs). The affinity of the interaction with p:MHCII plays a role in differentiation by mechanisms that are not completely understood. We found low-affinity TCRs biased mouse naive become follicular helper (Tfh) cells, whereas higher-affinity promoted formation Th1 or Th17 cells. explored basis for this phenomenon focusing IL-2R...
Influenza A virus (IAV) is a respiratory pathogen that has caused significant mortality throughout history and remains global threat to human health. Although much known about IAV replication, the regulation of replication dynamics not completely understood.
Abstract The magnitude of SARS-CoV-2–specific T cell responses correlates inversely with human disease severity, suggesting involvement in primary control. Whereas many COVID-19 vaccines focus on establishing humoral immunity to viral spike protein, vaccine-elicited may bolster durable protection or cross-reactivity variants. To better enable mechanistic and vaccination studies mice, we identified a dominant CD8 SARS-CoV-2 nucleoprotein epitope. Infection ACE2 transgenic mice elicited robust...
ABSTRACT Specific pathogen-free (SPF) laboratory mice dominate preclinical studies for immunology and vaccinology. Unfortunately, SPF often fail to accurately model human responses vaccination other immunological perturbations. Several groups have taken different approaches introduce additional microbial experience better immune experience. How these models compare is unknown. Here, we directly three models: housing in a microbe-rich barn-like environment (feralizing), adding wild-caught the...
A coordinated innate and adaptive immune response, orchestrated by antigen presenting cells (APCs), is required for effective clearance of influenza virus (IAV). Although IAV primarily infects epithelial the upper respiratory tract, APCs are also susceptible. To determine if transcription in these to generate protective responses, we engineered be selectively attenuated hematopoietic origin. Incorporation hematopoietic-specific miR-142 target sites into nucleoprotein effectively silenced...
Immunological changes associated with age contribute to the high rates of influenza virus morbidity and mortality in elderly. Compounding this problem, aged individuals do not respond vaccination as well younger, healthy adults. Efforts increase protection demographic group are utmost importance, proportion population above 65 is projected coming decade. Using a live truncated nonstructural protein 1 (NS1), we able stimulate cellular humoral immune responses mice comparable levels seen young...