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Principal Investigator: Antonella Casola
Organization: UNIVERSITY OF TEXAS MED BR GALVESTON
Fiscal Year: 2019
Award: $237,000
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
Acute respiratory tract infections are a leading cause of morbidity and mortality in children worldwide.
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, elderly and in
immunocompromised patients, as well as of asthma exacerbations. No effective treatment or vaccine for RSV
is currently available, and many fundamental questions regarding the pathogenesis of RSV-induced lung
disease have yet to be answered. Exosomes are microvesicles which in recent years have been shown to
transfer biologically active proteins, lipids and nucleic acids, and therefore participate in cell to cell
communication, inflammation, antigen presentation, programmed cell death, and disease pathogenesis. In
recent investigations, we found that RSV induces significant changes in exosomal RNA cargo composition, as
exosomes isolated from RSV-infected cells carry both viral proteins and viral RNA along with host mRNA and
rRNA fragments, as well as small non-coding RNAs (sncRNAs), such as miRNAs, piRNAs and tRNAs, in a
proportion different from exosomes isolated from mock-infected cells. Exosome-mediated export of host/viral
components may have variety of outcomes, serving both as a viral strategy to evade pathogen sensing in
infected cells and host strategy to induce innate responses in neighboring uninfected cells. In this application,
we will investigate whether epithelial-derived exosomes modulate innate immune responses and viral
replication using in vitro and in vivo models of RSV infection, and we will identify targets of novel sncRNAs
enriched in epithelial-derived exosomes in response to viral infection. A better understanding of how exosomes
may influence disease pathogenesis by facilitating or inhibiting immune responses in the course of RSV
infection will provide valuable insights into host-pathogen interactions and possibly identify novel targets for
therapy.
Terms: <0-11 years old><Acute><Affect><Antigen Presentation><Antiviral Agents><Antiviral Drugs><Antivirals><Apoptosis><Apoptosis Pathway><Assay><Asthma><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Bioassay><Biologic Assays><Biological><Biological Assay><Bronchial Asthma><Bronchioalveolar Lavage><Bronchiolitis><Bronchoalveolar Lavage><Bronchopulmonary Lavage><Burkitt Herpesvirus><Burkitt Lymphoma Virus><Candidate Disease Gene><Candidate Gene><Cell Body><Cell Communication><Cell Communication and Signaling><Cell Interaction><Cell Signaling><Cell to Cell Communication and Signaling><Cell-Cell Signaling><Cell-to-Cell Interaction><Cells><Cessation of life><Child><Child Youth><Children (0-21)><Clinical><Data><Death><Dendritic Cells><Development><Disease><Disorder><E-B Virus><EB virus><EBV><Elderly><Epithelial><Epithelial Cells><Epstein Barr Virus><Epstein-Barr Virus><Functional RNA><Gene Transcription><General Viruses><Generations><Genes><Genetic Transcription><HCV><HCV infection><HHV-4><HIV-1><HIV-I><HIV1><Hepatitis C><Hepatitis C virus><Hepatitis C virus infection><Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted><Hepatitus C><Human Herpesvirus 4><Human Immunodeficiency Virus Type 1><Human immunodeficiency virus 1><Immune><Immune Evasion><Immune response><Immunes><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunological response><Immunomodulation><Immunosuppressed Host><In Vitro><Infection><Infectious Mononucleosis Virus><Inflammation><Innate Immune Response><Interferon Type I><Intracellular Communication and Signaling><Investigation><Lead><Link><Lipids><Lower Respiratory Tract Infection><Lower respiratory infection><Lung Lavage><Lung damage><Lung diseases><Mediating><Messenger RNA><Methods><Mice><Mice Mammals><Micro RNA><MicroRNAs><Molecular><Morbidity><Morbidity - disease rate><Murine><Mus><Non-Coding><Non-Coding RNA><Non-Polyadenylated RNA><Non-translated RNA><Noncoding RNA><Nontranslated RNA><Nucleic Acids><Outcome><Pathogenesis><Pathway interactions><Pb element><Pharmacology><Play><Pneumonia><Production><Programmed Cell Death><Proteins><Public Health><Pulmonary Diseases><Pulmonary Disorder><RNA><RNA Expression><RNA Gene Products><RSV Vaccines><RSV infection><Reporter Genes><Respiratory Disease><Respiratory Infections><Respiratory Syncytial Virus Infections><Respiratory Syncytial Virus Vaccines><Respiratory System Disease><Respiratory System Disorder><Respiratory Tract Infections><Respiratory syncytial virus><Ribonucleic Acid><Ribosomal RNA><Role><SEQ-AN><Sequence Analyses><Sequence Analysis><Severities><Signal Transduction><Signal Transduction Systems><Signaling><Specificity><Syndrome><Testing><Time><Transcription><Transfer RNA><Transmission><Triplet Codon-Amino Acid Adaptor><Untranslated RNA><Vaccines><Veiled Cells><Viral><Viral Diseases><Viral Gene Products><Viral Gene Proteins><Viral Pathogenesis><Viral Proteins><Virus><Virus Diseases><Virus Replication><advanced age><anti-viral agents><anti-viral drugs><anti-virals><asthma attack><asthma exacerbation><biological signal transduction><bronchopulmonary lavage therapy><children><childrens'><developmental><disease of the lung><disorder of the lung><effective therapy><effective treatment><elders><exacerbation in asthma><exacerbation prone asthma><exacerbation prone asthmatic><exosome><flu><genomic RNA><geriatric><heavy metal Pb><heavy metal lead><hep C><hepatitis non A non B><host response><immune activation><immune modulation><immune regulation><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><immunosuppressed patient><improved><in vivo><in vivo Model><insight><intercellular communication><late life><later life><lung disorder><lung injury><mRNA><miRNA><miRNAs><microvesicles><mortality><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><next generation><non A, non B hepatitis><non-A, non-B hepatitis><noncoding><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><older adult><older person><pathogen><pathway><prevent><preventing><rRNA><recruit><respiratory><respiratory virus><response><senior citizen><social role><tRNA><transfer Ribonucleic acids><transmission process><viral RNA><viral infection><viral multiplication><viral replication><viral transmission><virus RNA><virus infection><virus multiplication><virus pathogenesis><virus protein><virus transmission><virus-induced disease><youngster>