Scholars@Duke
Stacy M. Horner

Stacy M. Horner

Associate Professor in Integrative Immunobiology
Integrative Immunobiology
stacy.horner@duke.edu
213 Research Drive, Room 0034 CARL Bldg, Durham, NC 27710

Selected Publications

UFMylation promotes orthoflavivirus infectious particle production.

Journal Article J Virol · June 3, 2025 Post-translational modifications play crucial roles in regulating viral infections, yet roles for many modifications remain unexplored in orthoflavivirus biology. Here, we demonstrate that the UFMylation system, a post-translational modification pathway th ... Full text Link to item Cite

Towards a Universal Translator: Decoding the PTMs That Regulate Orthoflavivirus Infection.

Journal Article Viruses · February 19, 2025 Post-translational modifications (PTMs) serve as critical regulators of protein function across biological systems, including during viral infection. For orthoflaviviruses, including human pathogens like dengue, Zika, and West Nile viruses, PTMs on viral p ... Full text Link to item Cite

Cellular RNA interacts with MAVS to promote antiviral signaling.

Journal Article Science · December 20, 2024 Antiviral signaling downstream of RIG-I-like receptors (RLRs) proceeds through a multi-protein complex organized around the adaptor protein mitochondrial antiviral signaling protein (MAVS). Protein complex function can be modulated by RNA molecules that pr ... Full text Link to item Cite

Programmable protein expression using a genetically encoded m6A sensor.

Journal Article Nat Biotechnol · September 2024 The N6-methyladenosine (m6A) modification is found in thousands of cellular mRNAs and is a critical regulator of gene expression and cellular physiology. m6A dysregulation contributes to several human diseases, and the m6A methyltransferase machinery has e ... Full text Link to item Cite

Recent insights into N6-methyladenosine during viral infection.

Journal Article Curr Opin Genet Dev · August 2024 The RNA modification of N6-methyladenosine (m6A) controls many aspects of RNA function that impact biological processes, including viral infection. In this review, we highlight recent work that shapes our current understanding of the diverse mechanisms by ... Full text Link to item Cite

Challenges to mapping and defining m6A function in viral RNA.

Journal Article RNA · April 16, 2024 Viral RNA molecules contain multiple layers of regulatory information. This includes features beyond the primary sequence, such as RNA structures and RNA modifications, including N6-methyladenosine (m6A). Many recent studies have identified the presence an ... Full text Link to item Cite

Virology-the path forward.

Journal Article J Virol · January 23, 2024 In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avo ... Full text Link to item Cite

Modifying the antiviral innate immune response by selective writing, erasing, and reading of m6A on viral and cellular RNA.

Journal Article Cell Chem Biol · January 18, 2024 Viral infection and the antiviral innate immune response are regulated by the RNA modification m6A. m6A directs nearly all aspects of RNA metabolism by recruiting RNA-binding proteins that mediate the fate of m6A-containing RNA. m6A controls the antiviral ... Full text Link to item Cite

The Evil DExH/D: Chikungunya virus runs but cannot hide from DDX39A.

Journal Article Mol Cell · November 16, 2023 In this issue, Tapescu et al.1 identify DDX39A as a novel antiviral protein that acts on conserved features of alphavirus RNA to limit infection in an IFN-independent manner. ... Full text Link to item Cite

Virology under the Microscope-a Call for Rational Discourse.

Journal Article mSphere · 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 ... Full text Link to item Cite

Structure-first identification of RNA elements that regulate dengue virus genome architecture and replication.

Journal Article Proc Natl Acad Sci U S A · April 11, 2023 The genomes of RNA viruses encode the information required for replication in host cells both in their linear sequence and in complex higher-order structures. A subset of these RNA genome structures show clear sequence conservation, and have been extensive ... Full text Link to item Cite

Virology under the Microscope-a Call for Rational Discourse.

Journal Article mBio · 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 ... Full text Link to item Cite

Virology under the Microscope-a Call for Rational Discourse.

Journal Article J 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 ... Full text Link to item Cite

WTAP Targets the METTL3 m6A-Methyltransferase Complex to Cytoplasmic Hepatitis C Virus RNA to Regulate Infection.

Journal Article J Virol · November 23, 2022 Modification of the hepatitis C virus (HCV) positive-strand RNA genome by N6-methyladenosine (m6A) regulates the viral life cycle. This life cycle takes place solely in the cytoplasm, while m6A addition on cellular mRNA takes place in the nucleus. Thus, th ... Full text Link to item Cite

Signaling from the RNA sensor RIG-I is regulated by ufmylation.

Journal Article Proc Natl Acad Sci U S A · April 12, 2022 The RNA-binding protein RIG-I is a key initiator of the antiviral innate immune response. The signaling that mediates the antiviral response downstream of RIG-I is transduced through the adaptor protein MAVS and results in the induction of type I and III i ... Full text Open Access Link to item Cite

FTO Suppresses STAT3 Activation and Modulates Proinflammatory Interferon-Stimulated Gene Expression.

Journal Article J Mol Biol · March 30, 2022 Signaling initiated by type I interferon (IFN) results in the induction of hundreds of IFN-stimulated genes (ISGs). The type I IFN response is important for antiviral restriction, but aberrant activation of this response can lead to inflammation and autoim ... Full text Link to item Cite

How RNA modifications regulate the antiviral response.

Journal Article Immunol Rev · November 2021 Induction of the antiviral innate immune response is highly regulated at the RNA level, particularly by RNA modifications. Recent discoveries have revealed how RNA modifications play key roles in cellular surveillance of nucleic acids and in controlling ge ... Full text Link to item Cite

The m6A reader IMP2 directs autoimmune inflammation through an IL-17- and TNFα-dependent C/EBP transcription factor axis.

Journal Article Sci Immunol · July 2, 2021 Excessive cytokine activity underlies many autoimmune conditions, particularly through the interleukin-17 (IL-17) and tumor necrosis factor-α (TNFα) signaling axis. Both cytokines activate nuclear factor κB, but appropriate induction of downstream effector ... Full text Link to item Cite

RNA modification of an RNA modifier prevents self-RNA sensing.

Journal Article PLoS Biol · July 2021 A new study in PLOS Biology finds that interferon (IFN)-induced adenosine deaminase acting on RNA 1 (ADAR1) mRNA is N6-methyladenosine (m6A) modified to promote its translation, enabling ADAR1 to modify self-double-stranded RNAs (dsRNAs) generated during t ... Full text Link to item Cite

N6-Methyladenosine Regulates Host Responses to Viral Infection.

Journal Article Trends Biochem Sci · May 2021 Recent discoveries have revealed that, during viral infection, the presence of the RNA modification N6-methyladenosine (m6A) on viral and cellular RNAs has profound impacts on infection outcome. Although m6A directly regulates many viral RNA processes, its ... Full text Link to item Cite

Flipping the script: viral capitalization of RNA modifications.

Journal Article Brief Funct Genomics · March 27, 2021 RNA encoded by RNA viruses is highly regulated so that it can function in multiple roles during the viral life cycle. These roles include serving as the mRNA template for translation or the genetic material for replication as well as being packaged into pr ... Full text Link to item Cite

Post-transcriptional regulation of antiviral gene expression by N6-methyladenosine.

Journal Article Cell Rep · March 2, 2021 Type I interferons (IFNs) induce hundreds of IFN-stimulated genes (ISGs) in response to viral infection. Induction of these ISGs must be regulated for an efficient and controlled antiviral response, but post-transcriptional controls of these genes have not ... Full text Link to item Cite

Direct RNA sequencing reveals m6A modifications on adenovirus RNA are necessary for efficient splicing.

Journal Article Nat Commun · November 26, 2020 Adenovirus is a nuclear replicating DNA virus reliant on host RNA processing machinery. Processing and metabolism of cellular RNAs can be regulated by METTL3, which catalyzes the addition of N6-methyladenosine (m6A) to mRNAs. While m6A-modified adenoviral ... Full text Link to item Cite

Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact.

Journal Article Cell · November 25, 2020 Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA's GeneL ... Full text Link to item Cite

The mRNA Cap 2'-O-Methyltransferase CMTR1 Regulates the Expression of Certain Interferon-Stimulated Genes.

Journal Article mSphere · May 13, 2020 Type I interferons (IFN) initiate an antiviral state through a signal transduction cascade that leads to the induction of hundreds of IFN-stimulated genes (ISGs) to restrict viral infection. Recently, RNA modifications on both host and viral RNAs have been ... Full text Link to item Cite

Limits in the detection of m6A changes using MeRIP/m6A-seq.

Journal Article Sci Rep · April 20, 2020 Many cellular mRNAs contain the modified base m6A, and recent studies have suggested that various stimuli can lead to changes in m6A. The most common method to map m6A and to predict changes in m6A between conditions is methylated RNA immunoprecipitation s ... Full text Link to item Cite

IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.

Journal Article Sci Adv · April 2020 In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cuta ... Full text Link to item Cite

Altered m6A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection.

Journal Article Mol Cell · February 6, 2020 The RNA modification N6-methyladenosine (m6A) modulates mRNA fate and thus affects many biological processes. We analyzed m6A across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C vir ... Full text Link to item Cite

Hepatitis C Virus Infection Is Inhibited by a Noncanonical Antiviral Signaling Pathway Targeted by NS3-NS4A.

Journal Article J Virol · December 1, 2019 The hepatitis C virus (HCV) NS3-NS4A protease complex is required for viral replication and is the major viral innate immune evasion factor. NS3-NS4A evades antiviral innate immunity by inactivating several proteins, including MAVS, the signaling adaptor f ... Full text Link to item Cite

Methods and Tools for MeRIP-Seq and Nanopore Detection of m6A(m) Changes.

Journal Article J Biomol Tech · December 2019 Previous studies have reported that various stimuli, including viral infection, cancer, and heat shock, lead to changes to m6A methylation of mRNAs from global increases or decreases in m6A to shifts in the distribution of methylation over transcripts or c ... Link to item Cite

Regulation of Viral Infection by the RNA Modification N6-Methyladenosine.

Journal Article Annu Rev Virol · September 29, 2019 In recent years, the RNA modification N6-methyladenosine (m6A) has been found to play a role in the life cycles of numerous viruses and also in the cellular response to viral infection. m6A has emerged as a regulator of many fundamental aspects of RNA biol ... Full text Link to item Cite

The small GTPase RAB1B promotes antiviral innate immunity by interacting with TNF receptor-associated factor 3 (TRAF3).

Journal Article J Biol Chem · September 27, 2019 Innate immune detection of viral nucleic acids during viral infection activates a signaling cascade that induces type I and type III IFNs as well as other cytokines, to generate an antiviral response. This signaling is initiated by pattern recognition rece ... Full text Link to item Cite

The acidic domain of the hepatitis C virus NS4A protein is required for viral assembly and envelopment through interactions with the viral E1 glycoprotein.

Journal Article PLoS Pathog · February 2019 Hepatitis C virus (HCV) assembly and envelopment are coordinated by a complex protein interaction network that includes most of the viral structural and nonstructural proteins. While the nonstructural protein 4A (NS4A) is known to be important for viral pa ... Full text Link to item Cite

Measuring Hepatitis C Virus Envelopment by Using a Proteinase K Protection Assay.

Journal Article Methods Mol Biol · 2019 The infectious virion of hepatitis C virus (HCV) is made up of the viral nucleocapsid surrounded by an envelope that contains an ER-derived membrane bilayer, cellular lipids, and the viral E1 and E2 glycoproteins. Because the infectious HCV particle contai ... Full text Link to item Cite

Pervasive tertiary structure in the dengue virus RNA genome.

Journal Article Proc Natl Acad Sci U S A · November 6, 2018 RNA virus genomes are efficient and compact carriers of biological information, encoding information required for replication both in their primary sequences and in higher-order RNA structures. However, the ubiquity of RNA elements with higher-order folds- ... Full text Link to item Cite

N6-methyladenosine modification of hepatitis B virus RNA differentially regulates the viral life cycle.

Journal Article Proc Natl Acad Sci U S A · August 28, 2018 N6-methyladenosine (m6A) RNA methylation is the most abundant epitranscriptomic modification of eukaryotic messenger RNAs (mRNAs). Previous reports have found m6A on both cellular and viral transcripts and defined its role in regulating numerous biological ... Full text Link to item Cite

An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease.

Journal Article Cell Host Microbe · August 8, 2018 Pathogens have been a strong driving force for natural selection. Therefore, understanding how human genetic differences impact infection-related cellular traits can mechanistically link genetic variation to disease susceptibility. Here we report the Hi-HO ... Full text Open Access Link to item Cite

A potentially abundant junctional RNA motif stabilized by m6A and Mg2.

Journal Article Nat Commun · July 17, 2018 N6-Methyladenosine (m6A) is an abundant post-transcriptional RNA modification that influences multiple aspects of gene expression. In addition to recruiting proteins, m6A can modulate RNA function by destabilizing base pairing. Here, we show that when neig ... Full text Link to item Cite

A Fluorescent Cell-Based System for Imaging Zika Virus Infection in Real-Time.

Journal Article Viruses · February 24, 2018 Zika virus (ZIKV) is a re-emerging flavivirus that is transmitted to humans through the bite of an infected mosquito or through sexual contact with an infected partner. ZIKV infection during pregnancy has been associated with numerous fetal abnormalities, ... Full text Link to item Cite

The acidic domain of the hepatitis C virus NS4A protein is required for viral assembly and envelopment through interactions with the viral E1 glycoprotein

Journal Article · 2018 Hepatitis C virus (HCV) assembly and envelopment are coordinated by a complex protein interaction network that includes most of the viral structural and nonstructural proteins. While the nonstructural protein 4A (NS4A) is known to be important for viral pa ... Full text Cite

RNA modifications go viral.

Journal Article PLoS Pathog · March 2017 Full text Link to item Cite

Protect this house: cytosolic sensing of viruses.

Journal Article Curr Opin Virol · February 2017 The ability to recognize invading viral pathogens and to distinguish their components from those of the host cell is critical to initiate the innate immune response. The efficiency of this detection is an important factor in determining the susceptibility ... Full text Link to item Cite

Knotty Zika Virus Blocks Exonuclease to Produce Subgenomic Flaviviral RNAs.

Journal Article Cell Host Microbe · January 11, 2017 In a recent issue of Science, Akiyama et al. (2016) prove the existence of a pseudoknot that stabilizes a nuclease-resistant RNA structure in the 3' untranslated region of Zika virus. This reinforced structure blocks the 5'→3' exonuclease Xrn1 for the prod ... Full text Link to item Cite

Methods to Visualize MAVS Subcellular Localization.

Journal Article Methods Mol Biol · 2017 The mitochondrial antiviral signaling (MAVS) protein is a central adaptor protein required for antiviral innate immune signaling. To facilitate its roles in innate immunity, MAVS localizes to multiple intracellular membranous compartments, including the mi ... Full text Link to item Cite

Hepatitis-C-virus-induced microRNAs dampen interferon-mediated antiviral signaling.

Journal Article Nat Med · December 2016 Hepatitis C virus (HCV) infects 200 million people globally, and 60-80% of cases persist as a chronic infection that will progress to cirrhosis and liver cancer in 2-10% of patients. We recently demonstrated that HCV induces aberrant expression of two host ... Full text Link to item Cite

N6-Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection.

Journal Article Cell Host Microbe · November 9, 2016 The RNA modification N6-methyladenosine (m6A) post-transcriptionally regulates RNA function. The cellular machinery that controls m6A includes methyltransferases and demethylases that add or remove this modification, as well as m6A-binding YTHDF proteins t ... Full text Link to item Cite

Innate immune evasion strategies of DNA and RNA viruses.

Journal Article Curr Opin Microbiol · August 2016 Upon infection, both DNA and RNA viruses can be sensed by pattern recognition receptors (PRRs) in the cytoplasm or the nucleus to activate antiviral innate immunity. Sensing of viral products leads to the activation of a signaling cascade that ultimately r ... Full text Link to item Cite

Posttranscriptional m(6)A Editing of HIV-1 mRNAs Enhances Viral Gene Expression.

Journal Article Cell Host Microbe · May 11, 2016 Covalent addition of a methyl group to adenosine N(6) (m(6)A) is an evolutionarily conserved and common RNA modification that is thought to modulate several aspects of RNA metabolism. While the presence of multiple m(6)A editing sites on diverse viral RNAs ... Full text Link to item Cite

Cooperation between the Hepatitis C Virus p7 and NS5B Proteins Enhances Virion Infectivity.

Journal Article J Virol · November 2015 UNLABELLED: The molecular mechanisms that govern hepatitis C virus (HCV) assembly, release, and infectivity are still not yet fully understood. In the present study, we sequenced a genotype 2A strain of HCV (JFH-1) that had been cell culture adapted in Huh ... Full text Link to item Cite

Insights into antiviral innate immunity revealed by studying hepatitis C virus.

Journal Article Cytokine · August 2015 Experimental studies on the interactions of the positive strand RNA virus hepatitis C virus (HCV) with the host have contributed to several discoveries in the field of antiviral innate immunity. These include revealing the antiviral sensing pathways that l ... Full text Link to item Cite

MAVS Coordination of Antiviral Innate Immunity.

Journal Article J Virol · July 2015 RNA virus infection is sensed in the cytoplasm by the retinoic acid-inducible gene I (RIG-I)-like receptors. These proteins signal through the host adaptor protein MAVS to trigger the antiviral innate immune response. Here, we describe how MAVS subcellular ... Full text Link to item Cite

Proteomic analysis of mitochondrial-associated ER membranes (MAM) during RNA virus infection reveals dynamic changes in protein and organelle trafficking.

Journal Article PLoS One · 2015 RIG-I pathway signaling of innate immunity against RNA virus infection is organized between the ER and mitochondria on a subdomain of the ER called the mitochondrial-associated ER membrane (MAM). The RIG-I adaptor protein MAVS transmits downstream signalin ... Full text Link to item Cite

Activation and evasion of antiviral innate immunity by hepatitis C virus.

Journal Article J Mol Biol · March 20, 2014 Hepatitis C virus (HCV) chronically infects 130-170 million people worldwide and is a major public health burden. HCV is an RNA virus that infects hepatocytes within liver, and this infection is sensed as non-self by the intracellular innate immune respons ... Full text Link to item Cite

The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAs.

Journal Article Nat Immunol · January 2014 IFNL3, which encodes interferon-λ3 (IFN-λ3), has received considerable attention in the hepatitis C virus (HCV) field, as many independent genome-wide association studies have identified a strong association between polymorphisms near IFNL3 and clearance o ... Full text Link to item Cite

Activation and evasion of antiviral innate immunity by hepatitis c virus

Journal Article Journal of Molecular Biology · 2014 Cite

Hepatitis C Virus. Strategies to Evade Antiviral Responses.

Journal Article Future Virol · 2014 Hepatitis C virus (HCV) causes chronic liver disease and poses a major clinical and economic burden worldwide. HCV is an RNA virus that is sensed as non-self in the infected liver by host pattern recognition receptors, triggering downstream signaling to in ... Full text Link to item Cite

Regulation of hepatic innate immunity by hepatitis C virus.

Journal Article Nat Med · July 2013 Hepatitis C virus (HCV) is a global public health problem involving chronic infection of the liver, which can cause liver disease and is linked with liver cancer. Viral innate immune evasion strategies and human genetic determinants underlie the transition ... Full text Link to item Cite

The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity.

Journal Article Cell Host Microbe · May 17, 2012 RIG-I is a cytosolic pathogen recognition receptor that initiates immune responses against RNA viruses. Upon viral RNA recognition, antiviral signaling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. He ... Full text Link to item Cite

Control of innate immune signaling and membrane targeting by the Hepatitis C virus NS3/4A protease are governed by the NS3 helix α0.

Journal Article J Virol · March 2012 Hepatitis C virus (HCV) infection is sensed in the host cell by the cytosolic pathogen recognition receptor RIG-I. RIG-I signaling is propagated through its signaling adaptor protein MAVS to drive activation of innate immunity. However, HCV blocks RIG-I si ... Full text Link to item Cite

Convergent evolution of escape from hepaciviral antagonism in primates.

Journal Article PLoS Biol · 2012 The ability to mount an interferon response on sensing viral infection is a critical component of mammalian innate immunity. Several viruses directly antagonize viral sensing pathways to block activation of the host immune response. Here, we show that recu ... Full text Link to item Cite

Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus.

Journal Article Proc Natl Acad Sci U S A · August 30, 2011 RIG-I is a cytosolic pathogen recognition receptor that engages viral RNA in infected cells to trigger innate immune defenses through its adaptor protein MAVS. MAVS resides on mitochondria and peroxisomes, but how its signaling is coordinated among these o ... Full text Link to item Cite

Intracellular innate immune cascades and interferon defenses that control hepatitis C virus.

Journal Article J Interferon Cytokine Res · September 2009 Hepatitis C virus (HCV) is a global public health problem that mediates a persistent infection in nearly 200 million people. HCV is efficient in establishing chronicity due in part to the inefficiency of the host immune system in controlling and counteract ... Full text Link to item Cite

Senescence induced by repression of human papillomavirus oncogenes in cervical cancer cells

Chapter · January 1, 2008 The study of tumor viruses has provided many insights into fundamental cellular processes including cell-cycle control, signal transduction, proliferation, and apoptosis. Another important but poorly understood cellular process is replicative senescence, a ... Cite

The DNA binding domain of a papillomavirus E2 protein programs a chimeric nuclease to cleave integrated human papillomavirus DNA in HeLa cervical carcinoma cells.

Journal Article J Virol · June 2007 Viral DNA binding proteins that direct nucleases or other protein domains to viral DNA in lytically or latently infected cells may provide a novel approach to modulate viral gene expression or replication. Cervical carcinogenesis is initiated by high-risk ... Full text Link to item Cite

Repression of the human papillomavirus E6 gene initiates p53-dependent, telomerase-independent senescence and apoptosis in HeLa cervical carcinoma cells.

Journal Article J Virol · April 2004 Cervical cancer cells express high-risk human papillomavirus (HPV) E6 and E7 proteins. When both HPV oncogenes are repressed in HeLa cervical carcinoma cells, the dormant p53 and retinoblastoma (Rb) tumor suppressor pathways are activated, and the cells un ... Full text Link to item Cite

Visualization of retroviral replication in living cells reveals budding into multivesicular bodies.

Journal Article Traffic · November 2003 Retroviral assembly and budding is driven by the Gag polyprotein and requires the host-derived vacuolar protein sorting (vps) machinery. With the exception of human immunodeficiency virus (HIV)-infected macrophages, current models predict that the vps mach ... Full text Link to item Cite