The Viral Polymerase Complex Mediates the Interaction of Viral Ribonucleoprotein Complexes with Recycling Endosomes during Sendai Virus Assembly

Author:

Genoyer Emmanuelle1,Kulej Katarzyna23,Hung Chuan Tien4,Thibault Patricia A.4,Azarm Kristopher4,Takimoto Toru5,Garcia Benjamin A.67,Lee Benhur4ORCID,Lakdawala Seema8,Weitzman Matthew D.237ORCID,López Carolina B.1ORCID

Affiliation:

1. Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

2. Division of Protective Immunity and Division of Cancer Pathobiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

3. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

4. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

5. Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA

6. Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

7. Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

8. Department of Microbiology & Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Abstract

Paramyxoviruses are members of a family of viruses that include a number of pathogens imposing significant burdens on human health. In particular, human parainfluenza viruses are an important cause of pneumonia and bronchiolitis in children for which there are no vaccines or directly acting antivirals. These cytoplasmic replicating viruses bud from the plasma membrane and co-opt cellular endosomal recycling pathways to traffic viral ribonucleoprotein complexes from the cytoplasm to the membrane of infected cells. The viral proteins required for viral engagement with the recycling endosome pathway are still not known. Here, we used the model paramyxovirus Sendai virus, or murine parainfluenza virus 1, to investigate the role of viral proteins in this initial step of viral assembly. We found that the viral polymerase components large protein L and accessory protein C are necessary for engagement with recycling endosomes. These findings are important in identifying viral proteins as potential targets for development of antivirals.

Funder

National Science Foundation Graduate Research Fellowship Program

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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