Feline Leukemia Virus-B Envelope Together With its GlycoGag and Human Immunodeficiency Virus-1 Nef Mediate Resistance to Feline SERINC5 |
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| Institution: | 1. Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany;2. Laboratório de Virologia, Departamento de Microbiologia, Imunologia e Parasitologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil;3. Max von Pettenkofer Institute & Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, Germany;4. InBIO – Research Network in Biodiversity and Evolutionary Biology, CIBIO, Campus de Vairão, Universidade do Porto, Vairão, Portugal;5. Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal;6. Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA;1. Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA;2. Molecular Biology Institute, University of California, Los Angeles, CA, USA;1. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA;2. Department of Immunology, University of Washington, Seattle, WA 98109, USA;3. Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA;1. Institut Pasteur, Université de Paris, CNRS UMR 3569, Virus Sensing and Signaling Unit, F-75015 Paris, France;2. Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France;3. Institut Pasteur, Université de Paris, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit, F-75015 Paris, France;4. Institut Curie, PSL Research University, INSERM U932, Paris, France;5. Institut Pasteur, Université de Paris, CNRS UMR 2000, Insect-Virus Interactions Unit, F-75015 Paris, France;6. Institut Curie, PSL Research University, Department of Translational Research-Biophenics High-Content Screening Laboratory, Cell and Tissue Imaging Facility (PICT-IBiSA), Paris, France;7. Institut Pasteur, Université de Paris, CNRS UMR 3569, Viral Genomics and Vaccination Unit, F-75015 Paris, France |
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| Abstract: | Human SERINC5 (SER5) protein is a recently described restriction factor against human immunodeficiency virus-1 (HIV-1), which is antagonized by HIV-1 Nef protein. Other retroviral accessory proteins such as the glycosylated Gag (glycoGag) from the murine leukemia virus (MLV) can also antagonize SER5. In addition, some viruses escape SER5 restriction by expressing a SER5-insensitive envelope (Env) glycoprotein. Here, we studied the activity of human and feline SER5 on HIV-1 and on the two pathogenic retroviruses in cats, feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). HIV-1 in absence of Nef is restricted by SER5 from domestic cats and protected by its Nef protein. The sensitivity of feline retroviruses FIV and FeLV to human and feline SER5 is considerably different: FIV is sensitive to feline and human SER5 and lacks an obvious mechanism to counteract SER5 activity, while FeLV is relatively resistant to SER5 inhibition. We speculated that similar to MLV, FeLV-A or FeLV-B express glycoGag proteins and investigated their function against human and feline SER5 in wild type and envelope deficient virus variants. We found that the endogenous FeLV recombinant virus, FeLV-B but not wild type exogenous FeLV-A envelope mediates a strong resistance against human and feline SER5. GlycoGag has an additional but moderate role to enhance viral infectivity in the presence of SER5 that seems to be dependent on the FeLV envelope. These findings may explain, why in vivo FeLV-B has a selective advantage and causes higher FeLV levels in infected cats compared to infections of FeLV-A only. |
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| Keywords: | SERINC5 restriction factors glycoGag HIV-1 FIV |
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