title: Intranasal Delivery of Peptide-Morpholinos to Knockdown Influenza Host Factors in Mice.
abstract: Influenza viruses replicate primarily in the lung tissue of different host species. For efficient replication the virus utilizes host factors that are expressed in target cells. Cell-penetrating peptide-conjugated Morpholino oligomers (PPMOs) designed to target viral proteins have shown promising results as potential antiviral drugs in tissue culture and animal models. However, since viruses tend to have high rates of mutations, targeting viral proteins may result in viral escape mutants. An alternative approach to inhibit virus replication with PPMOs is to target host factors that are required for virus replication. Delivery of PPMO through the intranasal route has been shown to be effective in knockdown of host factors or microbial genes leading to protection against respiratory pathogens and reduced microbial burden. In addition, protective host innate antiviral immune responses in the lung can be studied by knockdown of immune signaling factors using PPMOs. Here we describe a successful approach using PPMOs to knockdown either proviral or antiviral host factors leading to changes in influenza virus replication in the lungs of mice, providing a tool to investigate immune responses and host-virus interactions in vivo.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA. rirajsba@utmb.edu.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rajsbaum
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007251:Influenza, Human; D051379:Mice; D060172:Morpholinos / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000821:virology; D000070584:Tripartite Motif Proteins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D057846:Cell-Penetrating Peptides; D060172:Morpholinos; D000070584:Tripartite Motif Proteins; C578076:TRIM6 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Antiviral activity; Influenza virus; Innate immune response; Intranasal administration; Knockdown of host proteins; Lung tissue; PPMO; Proviral factors; TRIM E3-ubiquitin ligase; TRIM6; UBR4