Dynamin-2 Stabilizes the HIV-1 Fusion Pore with a Low Oligomeric State
Daniel M. Jones,
Luis A. Alvarez,
Rory Nolan,
Margarita Ferriz,
Raquel Sainz Urruela,
Xènia Massana-Muñoz,
Hila Novak-Kotzer,
Michael L. Dustin,
Sergi Padilla-Parra
Affiliations
Daniel M. Jones
Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK
Luis A. Alvarez
Wellcome Trust Human Genetics, Cellular Imaging Core, University of Oxford, Oxford OX3 7BN, UK
Rory Nolan
Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK
Margarita Ferriz
Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK
Raquel Sainz Urruela
Wellcome Trust Human Genetics, Cellular Imaging Core, University of Oxford, Oxford OX3 7BN, UK
Xènia Massana-Muñoz
Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK
Hila Novak-Kotzer
The Kennedy Institute of Rheumatology, University of Oxford, Headington, Oxford OX3 7BN, UK
Michael L. Dustin
The Kennedy Institute of Rheumatology, University of Oxford, Headington, Oxford OX3 7BN, UK
Sergi Padilla-Parra
Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK; Wellcome Trust Human Genetics, Cellular Imaging Core, University of Oxford, Oxford OX3 7BN, UK; Corresponding author
Summary: One of the key research areas surrounding HIV-1 concerns the regulation of the fusion event that occurs between the virus particle and the host cell during entry. Even if it is universally accepted that the large GTPase dynamin-2 is important during HIV-1 entry, its exact role during the first steps of HIV-1 infection is not well characterized. Here, we have utilized a multidisciplinary approach to study the DNM2 role during fusion of HIV-1 in primary resting CD4 T and TZM-bl cells. We have combined advanced light microscopy and functional cell-based assays to experimentally assess the role of dynamin-2 during these processes. Overall, our data suggest that dynamin-2, as a tetramer, might help to establish hemi-fusion and stabilizes the pore during HIV-1 fusion. : Regulation of HIV-1 fusion is one of the research areas of intense interest. Here, Jones et al. show that the large GTPase dynamin-2 (DNM2) forms a tetramer that acts to stabilize the HIV fusion pore. Keywords: HIV-1 fusion, Dynamin-2, advanced light imaging, number and brightness, cell-cell fusion
