Journal articleGenome Biol · July 18, 2026
BACKGROUND: Realizing the full potential of human genetics requires identifying causal variants and genes underlying association signals. Molecular quantitative trait locus (molQTL) analyses, such as expression QTL (eQTL) and splicing QTL (sQTL), link gene ...
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Journal articlemBio · June 10, 2026
UNLABELLED: Antiviral defenses at mucosal barriers are essential for preventing viral entry and systemic infection. Interferon epsilon (IFNε) is a unique type I IFN that, unlike other family members, is not induced by infection but is constitutively expres ...
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Journal articlemBio · June 10, 2026
UNLABELLED: Coronaviruses (CoVs) replicate their RNA genomes with a higher degree of fidelity than other RNA viruses, a mechanism mediated by the proofreading and recombination activities of the exoribonuclease domain of replicase nonstructural protein 14 ...
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Journal articleCell Stem Cell · April 2, 2026
Genomic modifications underlie the evolution of human brain features, including a larger neocortex. Human accelerated regions (HARs) are highly conserved loci containing human-specific variants, with ∼50% identified as neurodevelopmental enhancers. However ...
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Journal articleProc Natl Acad Sci U S A · March 10, 2026
Sialic acid is an abundant terminal glycan found on the surface of almost all mammalian cells and is utilized by many viruses as an attachment factor and/or bona fide receptor. Altering canonical cellular glycosylation can affect the ability of viruses to ...
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Journal articleActa Biomater · January 2026
Influenza presents a global threat representing hundreds of thousands of deaths each year worldwide, yet influenza vaccines currently do not offer full protection against infection and must be updated each year to account for antigenic drift. Subunit vacci ...
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Journal articleElife · November 28, 2025
A central signal that marshals host defense against many infections is the lymphocyte-derived cytokine interferon-gamma (IFNγ). The IFNγ receptor is expressed on most human cells, and its activation leads to the expression of antimicrobial proteins that ex ...
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Journal articleJ Virol · August 19, 2025
UNLABELLED: Effective vaccines are an important public health tool which may be needed to combat the emerging, highly pathogenic H5N1 avian influenza viruses currently circulating in cattle and poultry in the United States. While nucleic acid-based vaccine ...
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Journal articleJ Virol · February 25, 2025
Coronaviruses (CoVs) encode non-structural proteins (nsp's) 1-16, which assemble to form replication-transcription complexes that function in viral RNA synthesis. All CoVs encode a proofreading 3'-5' exoribonuclease in non-structural protein 14 (nsp14-ExoN ...
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Journal articlemBio · February 5, 2025
UNLABELLED: Respiratory epithelial cells can survive direct infection by influenza viruses, and the long-term consequences of that infection have been characterized in a subset of proximal airway cell types. The impact on the cells that survive viral infec ...
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Journal articlePLoS Pathog · January 2025
One approach for developing a more universal influenza vaccine is to elicit strong immune responses against canonically immunosubdominant epitopes in the surface exposed viral glycoproteins. While standard vaccines typically induce responses directed prima ...
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Journal articleJ Virol · November 19, 2024
In early 2024, a clade 2.3.4.4b high pathogenic H5N1 avian influenza virus was detected in dairy cows and humans in the United States. Since then, it has spread to herds in at least 13 states and caused symptomatic disease in at least fifteen people. To fa ...
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Journal articleJ Virol · October 22, 2024
Seasonal influenza vaccines provide mostly strain-specific protection due to the elicitation of antibody responses focused on evolutionarily plastic antigenic sites in the hemagglutinin head domain. To direct the humoral response toward more conserved epit ...
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Journal articleNat Commun · October 8, 2024
Influenza viruses cause substantial morbidity and mortality every year despite seasonal vaccination. mRNA-based vaccines have the potential to elicit more protective immune responses, but for maximal breadth and durability, it is desirable to deliver both ...
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Journal articlePLoS Pathog · July 2024
The CRISPR-Cas13 system has been proposed as an alternative treatment of viral infections. However, for this approach to be adopted as an antiviral, it must be optimized until levels of efficacy rival or exceed the performance of conventional approaches. T ...
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Journal articleSci Transl Med · May 2024
Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of the hemagglutinin (HA) glycoprotein. Because of viral antigenic drift at these sites, vaccines need to be update ...
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Journal articleJ Biol Chem · April 2024
The innate immune system features a web of interacting pathways that require exquisite regulation. To identify novel nodes in this immune landscape, we conducted a gain-of-function, genome-wide CRISPR activation screen with influenza A virus. We identified ...
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Journal articleMicrobiol Spectr · October 17, 2023
Clustered regularly interspaced short palindromic repeats (CRISPR)-based technologies have already begun to revolutionize biomedical science. An emerging application of this technology is in the development of genetically modified model organisms to study ...
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Journal articleAnnu Rev Virol · September 29, 2023
Negative-stranded RNA viruses are a large group of viruses that encode their genomes in RNA across multiple segments in an orientation antisense to messenger RNA. Their members infect broad ranges of hosts, and there are a number of notable human pathogens ...
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Journal articleElife · September 7, 2023
The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of pro ...
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Journal articleJ Virol · August 31, 2023
Multiple coronaviruses (CoVs) can cause respiratory diseases in humans. While prophylactic vaccines designed to prevent infection are available for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), incomplete vaccine efficacy, vaccine hesitancy ...
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Journal articlemSphere · April 20, 2023
Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. D ...
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Journal articlemBio · February 28, 2023
Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. D ...
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Journal articleJ Virol · February 28, 2023
Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. D ...
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Journal articleCell Genom · November 9, 2022
During pandemics, individuals exhibit differences in risk and clinical outcomes. Here, we developed single-cell high-throughput human in vitro susceptibility testing (scHi-HOST), a method for rapidly identifying genetic variants that confer resistance and ...
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Journal articleNat Commun · October 29, 2022
Communicable respiratory viral infections pose both epidemic and pandemic threats and broad-spectrum antiviral strategies could improve preparedness for these events. To discover host antiviral restriction factors that may act as suitable targets for the d ...
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Journal articleCell Rep · October 25, 2022
The cellular fate after infection with human coronaviruses (HCoVs) is typically death. Previous data suggest, however, that the transcriptional state of an individual cell may sometimes allow additional outcomes of infection. Here, to probe the range of in ...
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Journal articleSci Signal · October 25, 2022
Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccin ...
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Journal articleStem Cell Reports · September 13, 2022
In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be establish ...
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Journal articleJ Virol · August 10, 2022
Vaccines targeting SARS-CoV-2 have been shown to be highly effective; however, the breadth against emerging variants and the longevity of protection remains unclear. Postimmunization boosting has been shown to be beneficial for disease protection, and as n ...
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Journal articleJ Virol · July 27, 2022
Influenza virus infections are thought to be initiated in a small number of cells; however, the heterogeneity across the cellular responses of the epithelial cells during establishment of disease is incompletely understood. Here, we used an H1N1 influenza ...
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Journal articleFEBS J · July 2022
The productive replication of human influenza viruses is almost exclusively restricted to cells in the respiratory tract. However, a key aspect of the host response to viral infection is the production of inflammatory cytokines and chemokines that are not ...
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Journal articleCurr Opin Virol · April 2022
Influenza viruses are simultaneously supported and antagonized by factors within the host cell. This close relationship is the theoretical basis for future antivirals that target the host rather than the virus itself, a concept termed host-directed therape ...
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Journal articleCancers (Basel) · February 12, 2022
Sex hormones, such as estrogen and testosterone, are steroid compounds with well-characterized effects on the coordination and development of vertebrate reproductive systems. Since their discovery, however, it has become clear that these "sex hormones" als ...
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Journal articlePLoS Pathog · September 2021
Influenza A viruses encode their genomes across eight, negative sense RNA segments. The six largest segments produce mRNA transcripts that do not generally splice; however, the two smallest segments are actively spliced to produce the essential viral prote ...
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Journal articleScience · August 20, 2021
There is an urgent need for antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We screened a library of 1900 clinically safe drugs against OC43, a human beta coronavirus that causes the common cold, and eval ...
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Journal articleSci Signal · July 13, 2021
The type I interferon (IFN) response is an important component of the innate immune response to viral infection. Precise control of IFN responses is critical because insufficient expression of IFN-stimulated genes (ISGs) can lead to a failure to restrict v ...
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Journal articlePLoS Pathog · May 2021
Antiviral therapeutics are a front-line defense against virally induced diseases. Because viruses frequently mutate to escape direct inhibition of viral proteins, there is interest in targeting the host proteins that the virus must co-opt to complete its r ...
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Journal articleJ Virol · April 26, 2021
The development of improved and universal anti-influenza vaccines would represent a major advance in the protection of human health. In order to facilitate the development of such vaccines, understanding how viral proteins can contribute to protection from ...
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Journal articleScience · January 15, 2021
Type I interferon (IFN) signaling in fetal tissues causes developmental abnormalities and fetal demise. Although pathogens that infect fetal tissues can induce birth defects through the local production of type I IFN, it remains unknown why systemic IFN ge ...
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Journal articleCell Stem Cell · December 3, 2020
Coronavirus infection causes diffuse alveolar damage leading to acute respiratory distress syndrome. The absence of ex vivo models of human alveolar epithelium is hindering an understanding of coronavirus disease 2019 (COVID-19) pathogenesis. Here, we repo ...
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Journal articleJ Virol · October 27, 2020
In late 2019, a human coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, likely from a zoonotic reservoir. This virus causes COVID-19, has infected millions of people, and has led to hundreds of thousands of de ...
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Journal articleCell Rep · September 1, 2020
Influenza viruses initiate infection in the upper respiratory tract (URT), but early viral tropism and the importance of cell-type-specific antiviral responses in this tissue remain incompletely understood. By infecting transgenic lox-stop-lox reporter mic ...
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Journal articleCell · May 14, 2020
The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based st ...
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Journal articleNat Microbiol · November 2019
Despite the cytopathic nature of influenza A virus (IAV) replication, we recently reported that a subset of lung epithelial club cells is able to intrinsically clear the virus and survive infection. However, the mechanisms that drive cell survival during a ...
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Journal articlePLoS Pathog · November 2019
Influenza A viruses (IAVs) encode their genome across eight, negative sense RNA segments. During viral assembly, the failure to package all eight segments, or packaging a mutated segment, renders the resulting virion incompletely infectious. It is known th ...
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Journal articlePLoS Pathog · September 2019
Influenza A virus (IAV) is a seasonal pathogen with the potential to cause devastating pandemics. IAV infects multiple epithelial cell subsets in the respiratory tract, eliciting damage to the lungs. Clearance of IAV is primarily dependent on CD8+ T cells, ...
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Journal articleViruses · August 9, 2019
Influenza B viruses (IBVs) are major contributors to total human influenza disease, responsible for ~1/3 of all infections. These viruses, however, are relatively less studied than the related influenza A viruses (IAVs). While it has historically been assu ...
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Journal articleNat Commun · February 15, 2019
Influenza B virus (IBV) is an acute, respiratory RNA virus that has been assumed to induce the eventual death of all infected cells. We and others have shown however, that infection with apparently cytopathic viruses does not necessarily lead to cell death ...
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Journal articleJ Virol · August 15, 2018
Influenza A and B viruses can continuously evade humoral immune responses by developing mutations in the globular head of the hemagglutinin (HA) that prevent antibody binding. However, the influenza B virus HA over time displays less antigenic variation de ...
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Journal articleVaccines (Basel) · March 30, 2018
Influenza viruses infect approximately 20% of the global population annually, resulting in hundreds of thousands of deaths. While there are Food and Drug Administration (FDA) approved antiviral drugs for combating the disease, vaccination remains the best ...
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Journal articleCell Host Microbe · September 13, 2017
Many viral RNAs are modified by methylation of the N6 position of adenosine (m6A). m6A is thought to regulate RNA splicing, stability, translation, and secondary structure. Influenza A virus (IAV) expresses m6A-modified RNAs, but the effects of m6A on this ...
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Journal articleCell Rep · August 15, 2017
Influenza A virus (IAV) is a pathogen that poses significant risks to human health. It is therefore critical to develop strategies to prevent influenza disease. Many loss-of-function screens have been performed to identify the host proteins required for vi ...
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Journal articlemBio · June 6, 2017
Influenza virus vaccine production is currently limited by the ability to grow circulating human strains in chicken eggs or in cell culture. To facilitate cost-effective growth, vaccine strains are serially passaged under production conditions, which frequ ...
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Journal articleProc Natl Acad Sci U S A · April 5, 2016
A brief window of antigen-nonspecific protection has been observed after influenza A virus (IAV) infection. Although this temporary immunity has been assumed to be the result of residual nonspecific inflammation, this period of induced immunity has not bee ...
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Journal articleImmunity · January 19, 2016
Viruses are obligate parasites and thus require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy hosts use to suppress viral replication and a potential pan-antiviral therapy. To define ...
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Journal articleJ Virol · December 2015
Influenza B virus is a human pathogen responsible for significant health and economic burden. Research into this pathogen has been limited by the lack of reporter viruses. Here we describe the development of both a replication-competent fluorescent influen ...
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Journal articleCell Rep · June 9, 2015
Measles virus undergoes error-prone replication like other RNA viruses, but over time, it has remained antigenically monotypic. The constraints on the virus that prevent the emergence of antigenic variants are unclear. As a first step in understanding this ...
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Journal articleJ Exp Med · August 25, 2014
Respiratory infection of influenza A virus (IAV) is frequently characterized by extensive immunopathology and proinflammatory signaling that can persist after virus clearance. In this report, we identify cells that become infected, but survive, acute influ ...
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Journal articleProc Natl Acad Sci U S A · December 10, 2013
The molecular basis for the diversity across influenza strains is poorly understood. To gain insight into this question, we mutagenized the viral genome and sequenced recoverable viruses. Only two small regions in the genome were enriched for insertions, t ...
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Journal articleMol Biosyst · December 2013
Hepatitis C virus (HCV) alters the global behavior of the host cell to create an environment conducive to its own replication, but much remains unknown about how HCV proteins elicit these changes. Thus, a better understanding of the interface between the v ...
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Journal articleJ Virol · October 2013
Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin), and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly elicitin ...
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Journal articleJ Virol · August 2013
Influenza A virus is a major human pathogen responsible for seasonal epidemics as well as pandemic outbreaks. Due to the continuing burden on human health, the need for new tools to study influenza virus pathogenesis as well as to evaluate new therapeutics ...
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Journal articlePLoS Pathog · 2013
The Influenza A virus genome consists of eight negative sense, single-stranded RNA segments. Although it has been established that most virus particles contain a single copy of each of the eight viral RNAs, the packaging selection mechanism remains poorly ...
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Journal articleCurr Opin Microbiol · August 2012
Viruses physically and metabolically remodel the host cell to establish an optimal environment for their replication. Many of these processes involve the manipulation of lipid signaling, synthesis, and metabolism. An emerging theme is that these lipid-modi ...
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Journal articlePLoS Pathog · January 2012
The current model of hepatitis C virus (HCV) production involves the assembly of virions on or near the surface of lipid droplets, envelopment at the ER in association with components of VLDL synthesis, and egress via the secretory pathway. However, the ce ...
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Journal articleMol Cell Proteomics · December 2011
Dengue virus (DENV), an emerging mosquito-transmitted pathogen capable of causing severe disease in humans, interacts with host cell factors to create a more favorable environment for replication. However, few interactions between DENV and human proteins h ...
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Journal articleViruses · August 2011
Several independent groups have published that autophagy is required for optimal RNA replication of dengue virus (DENV). Initially, it was postulated that autophagosomes might play a structural role in replication complex formation. However, cryo-EM tomogr ...
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Journal articleTrends Microbiol · July 2011
Viruses have evolved complex and dynamic interactions with their host cell. In recent years we have gained insight into the expanding roles for host lipids in the virus life cycle. In particular, viruses target lipid signaling, synthesis, and metabolism to ...
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Journal articleCell Host Microbe · November 18, 2010
Autophagy influences numerous cellular processes, including innate and adaptive immunity against intracellular pathogens. However, some viruses, including dengue virus (DENV), usurp autophagy to enhance their replication. The mechanism for a positive role ...
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Journal articleProc Natl Acad Sci U S A · October 5, 2010
Dengue virus (DENV) modifies cellular membranes to establish its sites of replication. Although the 3D architecture of these structures has recently been described, little is known about the cellular pathways required for their formation and expansion. In ...
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Journal articlePLoS Pathog · December 2009
Hepatitis C virus (HCV) enters hepatocytes following a complex set of receptor interactions, culminating in internalization via clathrin-mediated endocytosis. However, aside from receptors, little is known about the cellular molecular requirements for infe ...
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Journal articleProc Natl Acad Sci U S A · May 5, 2009
Hepatitis C virus (HCV) reorganizes cellular membranes to establish sites of replication. The required host pathways and the mechanism of cellular membrane reorganization are poorly characterized. Therefore, we interrogated a customized small interfering R ...
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Journal articleJ Vasc Res · 2008
BACKGROUND: The success of peripheral vein grafts is limited by intimal hyperplasia. Transforming growth factor (TGF)-beta(1) has effects on cell proliferation, apoptosis and extracellular matrix synthesis. We have previously observed positive changes in v ...
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Journal articleJ Vasc Surg · May 2006
BACKGROUND: The main cause of occlusion and vein graft failure after peripheral and coronary arterial reconstruction is intimal hyperplasia. Transforming growth factor beta-1 (TGF-beta1) is a pleiotropic cytokine known to have powerful effects on cell grow ...
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