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      Drosophila as a Model for Infectious Diseases

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          Abstract

          The fruit fly, Drosophila melanogaster, has been used to understand fundamental principles of genetics and biology for over a century. Drosophila is now also considered an essential tool to study mechanisms underlying numerous human genetic diseases. In this review, we will discuss how flies can be used to deepen our knowledge of infectious disease mechanisms in vivo. Flies make effective and applicable models for studying host-pathogen interactions thanks to their highly conserved innate immune systems and cellular processes commonly hijacked by pathogens. Drosophila researchers also possess the most powerful, rapid, and versatile tools for genetic manipulation in multicellular organisms. This allows for robust experiments in which specific pathogenic proteins can be expressed either one at a time or in conjunction with each other to dissect the molecular functions of each virulent factor in a cell-type-specific manner. Well documented phenotypes allow large genetic and pharmacological screens to be performed with relative ease using huge collections of mutant and transgenic strains that are publicly available. These factors combine to make Drosophila a powerful tool for dissecting out host-pathogen interactions as well as a tool to better understand how we can treat infectious diseases that pose risks to public health, including COVID-19, caused by SARS-CoV-2.

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          Most cited references273

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          A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing

          SUMMARY The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption 1,2 . There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.
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            Characterization of a novel coronavirus associated with severe acute respiratory syndrome.

            P Rota (2003)
            In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.
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              New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer

              Epithelial-mesenchymal transition (EMT) is a cellular programme that is known to be crucial for embryogenesis, wound healing and malignant progression. During EMT, cell-cell and cell-extracellular matrix interactions are remodelled, which leads to the detachment of epithelial cells from each other and the underlying basement membrane, and a new transcriptional programme is activated to promote the mesenchymal fate. In the context of neoplasias, EMT confers on cancer cells increased tumour-initiating and metastatic potential and a greater resistance to elimination by several therapeutic regimens. In this Review, we discuss recent findings on the mechanisms and roles of EMT in normal and neoplastic tissues, and the cell-intrinsic signals that sustain expression of this programme. We also highlight how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state, which could function as cancer stem cells. In addition, we describe the contributions of the tumour microenvironment in inducing EMT and the effects of EMT on the immunobiology of carcinomas.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                08 March 2021
                March 2021
                : 22
                : 5
                : 2724
                Affiliations
                [1 ]Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jacob.Harnish@ 123456bcm.edu (J.M.H.); nichole.link@ 123456neuro.utah.edu (N.L.)
                [2 ]Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
                [3 ]Howard Hughes Medical Institute, Houston, TX 77030, USA
                [4 ]Department of Neuroscience, BCM, Houston, TX 77030, USA
                [5 ]Development, Disease Models and Therapeutics Graduate Program, BCM, Houston, TX 77030, USA
                Author notes
                [* ]Correspondence: yamamoto@ 123456bcm.edu ; Tel.: +1-832-824-8119
                [†]

                Current Affiliation: Department of Neurobiology, University of Utah, Salt Lake City, UT 84112, USA.

                Author information
                https://orcid.org/0000-0002-9410-6951
                https://orcid.org/0000-0003-2172-8036
                Article
                ijms-22-02724
                10.3390/ijms22052724
                7962867
                33800390
                8a74b8d2-ad9e-4073-b566-d12685e5219c
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 January 2021
                : 14 February 2021
                Categories
                Review

                Molecular biology
                drosophila melanogaster,immunity,infection,pathogens and virulence factors,disease models

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