Scholars@Duke
Brook Heaton

Brook Heaton

Assistant Research Professor of Molecular Genetics and Microbiology
Molecular Genetics and Microbiology
brook.heaton@duke.edu
GHRB 1021, Box 103020, Durham, NC 27710
GHRB 1021 BX103020, 905 S LaSalle St, Durham, NC 27710

Selected Publications

The coronavirus nsp14 exoribonuclease interface with the cofactor nsp10 is essential for efficient virus replication and enzymatic activity.

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

Fluorescent and bioluminescent bovine H5N1 influenza viruses for evaluation of antiviral interventions.

Journal Article Journal of virology · November 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 ... Full text Cite

Headless hemagglutinin-containing influenza viral particles direct immune responses toward more conserved epitopes.

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

A low-background, fluorescent assay to evaluate inhibitors of diverse viral proteases.

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

Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication.

Journal Article Sci 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 ... Full text Open Access Link to item Cite

Rapid tissue prototyping with micro-organospheres.

Journal Article Stem 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 ... Full text Open Access Link to item Cite

A Virion-Based Combination Vaccine Protects against Influenza and SARS-CoV-2 Disease in Mice.

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

TMEM41B is a host factor required for the replication of diverse coronaviruses including SARS-CoV-2.

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

Engineered influenza virions reveal the contributions of non-hemagglutinin structural proteins to vaccine mediated protection.

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

Human Lung Stem Cell-Based Alveolospheres Provide Insights into SARS-CoV-2-Mediated Interferon Responses and Pneumocyte Dysfunction.

Journal Article Cell 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 ... Full text Open Access Link to item Cite

Development of a Fluorescence-Based, High-Throughput SARS-CoV-2 3CLpro Reporter Assay.

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

DNA mismatch repair is required for the host innate response and controls cellular fate after influenza virus infection.

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

Mycobacterial Mutagenesis and Drug Resistance Are Controlled by Phosphorylation- and Cardiolipin-Mediated Inhibition of the RecA Coprotease.

Journal Article Mol Cell · October 4, 2018 Infection with Mycobacterium tuberculosis continues to cause substantial human mortality, in part because of the emergence of antimicrobial resistance. Antimicrobial resistance in tuberculosis is solely the result of chromosomal mutations that modify drug ... Full text Link to item Cite

A CRISPR Activation Screen Identifies a Pan-avian Influenza Virus Inhibitory Host Factor.

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

Rationally Designed Influenza Virus Vaccines That Are Antigenically Stable during Growth in Eggs.

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

Deficiency of double-strand DNA break repair does not impair Mycobacterium tuberculosis virulence in multiple animal models of infection.

Journal Article Infect Immun · August 2014 Mycobacterium tuberculosis persistence within its human host requires mechanisms to resist the effector molecules of host immunity, which exert their bactericidal effects through damaging pathogen proteins, membranes, and DNA. Substantial evidence indicate ... Full text Link to item Cite

Molecular structure and function of the novel BrnT/BrnA toxin-antitoxin system of Brucella abortus.

Journal Article J Biol Chem · April 6, 2012 Type II toxin-antitoxin (TA) systems are expressed from two-gene operons that encode a cytoplasmic protein toxin and its cognate protein antitoxin. These gene cassettes are often present in multiple copies on bacterial chromosomes, where they have been rep ... Full text Link to item Cite