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Nat Commun. 2020 Jan 7;11(1):23. doi: 10.1038/s41467-019-13838-3. [h=1]Quantitative live cell imaging reveals influenza virus manipulation of Rab11A transport through reduced dynein association.[/h]
Bhagwat AR[SUP]1[/SUP], Le Sage V[SUP]1[/SUP], Nturibi E[SUP]1[/SUP], Kulej K[SUP]2[/SUP], Jones J[SUP]1[/SUP], Guo M[SUP]3[/SUP], Tae Kim E[SUP]2[/SUP], Garcia BA[SUP]4,[/SUP][SUP]5[/SUP], Weitzman MD[SUP]2,[/SUP][SUP]5,[/SUP][SUP]6[/SUP], Shroff H[SUP]3[/SUP], Lakdawala SS[SUP]7,[/SUP][SUP]8[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA. 2 The Children's Hospital of Philadelphia Research Institute, 3501 Civic Center Dr., Philadelphia, PA, 19104, USA. 3 Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, 13 South Drive, Building 13, Bethesda, MD, 20892, USA. 4 Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd, Building 421, Philadelphia, PA, 19104, USA. 5 Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, 3400, Civic Center Blvd, Philadelphia, PA, 19104, USA. 6 Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. 7 Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA. lakdawala@pitt.edu. 8 Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA. lakdawala@pitt.edu.
[h=3]Abstract[/h] Assembly of infectious influenza A viruses (IAV) is a complex process involving transport from the nucleus to the plasma membrane. Rab11A-containing recycling endosomes have been identified as a platform for intracellular transport of viral RNA (vRNA). Here, using high spatiotemporal resolution light-sheet microscopy (~1.4 volumes/second, 330 nm isotropic resolution), we quantify Rab11A and vRNA movement in live cells during IAV infection and report that IAV infection decreases speed and increases arrest of Rab11A. Unexpectedly, infection with respiratory syncytial virus alters Rab11A motion in a manner opposite to IAV, suggesting that Rab11A is a common host component that is differentially manipulated by respiratory RNA viruses. Using two-color imaging we demonstrate co-transport of Rab11A and IAV vRNA in infected cells and provide direct evidence that vRNA-associated Rab11A have altered transport. The mechanism of altered Rab11A movement is likely related to a decrease in dynein motors bound to Rab11A vesicles during IAV infection.
PMID: 31911620 DOI: 10.1038/s41467-019-13838-3
Free PMC Article
Bhagwat AR[SUP]1[/SUP], Le Sage V[SUP]1[/SUP], Nturibi E[SUP]1[/SUP], Kulej K[SUP]2[/SUP], Jones J[SUP]1[/SUP], Guo M[SUP]3[/SUP], Tae Kim E[SUP]2[/SUP], Garcia BA[SUP]4,[/SUP][SUP]5[/SUP], Weitzman MD[SUP]2,[/SUP][SUP]5,[/SUP][SUP]6[/SUP], Shroff H[SUP]3[/SUP], Lakdawala SS[SUP]7,[/SUP][SUP]8[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA. 2 The Children's Hospital of Philadelphia Research Institute, 3501 Civic Center Dr., Philadelphia, PA, 19104, USA. 3 Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, 13 South Drive, Building 13, Bethesda, MD, 20892, USA. 4 Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd, Building 421, Philadelphia, PA, 19104, USA. 5 Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, 3400, Civic Center Blvd, Philadelphia, PA, 19104, USA. 6 Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. 7 Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA. lakdawala@pitt.edu. 8 Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA. lakdawala@pitt.edu.
[h=3]Abstract[/h] Assembly of infectious influenza A viruses (IAV) is a complex process involving transport from the nucleus to the plasma membrane. Rab11A-containing recycling endosomes have been identified as a platform for intracellular transport of viral RNA (vRNA). Here, using high spatiotemporal resolution light-sheet microscopy (~1.4 volumes/second, 330 nm isotropic resolution), we quantify Rab11A and vRNA movement in live cells during IAV infection and report that IAV infection decreases speed and increases arrest of Rab11A. Unexpectedly, infection with respiratory syncytial virus alters Rab11A motion in a manner opposite to IAV, suggesting that Rab11A is a common host component that is differentially manipulated by respiratory RNA viruses. Using two-color imaging we demonstrate co-transport of Rab11A and IAV vRNA in infected cells and provide direct evidence that vRNA-associated Rab11A have altered transport. The mechanism of altered Rab11A movement is likely related to a decrease in dynein motors bound to Rab11A vesicles during IAV infection.
PMID: 31911620 DOI: 10.1038/s41467-019-13838-3
Free PMC Article