Conserved Eukaryotic Fusogens Can Fuse Viral Envelopes to Cells

A Caenorhabditis elegans cell-surface fusion protein can promote viral fusion with mammalian cells. Caenorhabditis elegans proteins AFF-1 and EFF-1 [C. elegans fusion family (CeFF) proteins] are essential for developmental cell-to-cell fusion and can merge insect cells. To study the structure and function of AFF-1, we constructed vesicular stomatitis virus (VSV) displaying AFF-1 on the viral envelope, substituting the native fusogen VSV glycoprotein. Electron microscopy and tomography revealed that AFF-1 formed distinct supercomplexes resembling pentameric and hexameric “flowers” on pseudoviruses. Viruses carrying AFF-1 infected mammalian cells only when CeFFs were on the target cell surface. Furthermore, we identified fusion family (FF) proteins within and beyond nematodes, and divergent members from the human parasitic nematode Trichinella spiralis and the chordate Branchiostoma floridae could also fuse mammalian cells. Thus, FF proteins are part of an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle.

[1]  J. Lepault,et al.  Distinct structural rearrangements of the VSV glycoprotein drive membrane fusion , 2010, The Journal of cell biology.

[2]  R. Rosenfeld.  Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[3]  Nicolas Vandewalle,et al.  Colloids and Surfaces A: Physicochemical and Engineering Aspects , 2009 .

[4]  H. McMahon,et al.  Mechanisms of membrane fusion: disparate players and common principles , 2008, Nature Reviews Molecular Cell Biology.

[5]  Kathryn L. Schornberg,et al.  Structures and Mechanisms of Viral Membrane Fusion Proteins: Multiple Variations on a Common Theme , 2008 .

[6]  L. Chernomordik,et al.  Viral and Developmental Cell Fusion Mechanisms: Conservation and Divergence , 2008, Developmental Cell.

[7]  Meital Oren-Suissa,et al.  Cell fusion during development. , 2007, Trends in cell biology.

[8]  Elizabeth H. Chen,et al.  Cell–cell fusion , 2007, FEBS letters.

[9]  L. Chernomordik,et al.  AFF-1, a FOS-1-regulated fusogen, mediates fusion of the anchor cell in C. elegans. , 2007, Developmental cell.

[10]  L. Chernomordik,et al.  The C. elegans developmental fusogen EFF-1 mediates homotypic fusion in heterologous cells and in vivo. , 2006, Developmental cell.

[11]  T. Mizutani,et al.  Vesicular stomatitis virus pseudotyped with severe acute respiratory syndrome coronavirus spike protein. , 2005, The Journal of general virology.

[12]  C. Glover,et al.  Gene expression profiling for hematopoietic cell culture , 2006 .

[13]  D. Hall,et al.  EFF-1 Is Sufficient to Initiate and Execute Tissue-Specific Cell Fusion in C. elegans , 2004, Current Biology.

[14]  J. Rothman,et al.  Fusion of Cells by Flipped SNAREs , 2003, Science.

[15]  John White,et al.  The type I membrane protein EFF-1 is essential for developmental cell fusion. , 2002, Developmental cell.

[16]  K. Ishii,et al.  Characterization of pseudotype VSV possessing HCV envelope proteins. , 2001, Virology.

[17]  J. Ashby.  References and Notes , 1999 .

[18]  A. Sanchez,et al.  A system for functional analysis of Ebola virus glycoprotein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Rose,et al.  Foreign glycoproteins expressed from recombinant vesicular stomatitis viruses are incorporated efficiently into virus particles. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[20]  C. Kenyon,et al.  The nematode Caenorhabditis elegans. , 1988, Science.

[21]  L. Lefrançois,et al.  The interaction of antibody with the major surface glycoprotein of vesicular stomatitis virus. I. Analysis of neutralizing epitopes with monoclonal antibodies. , 1982, Virology.

[22]  B. Bainbridge,et al.  Genetics , 1981, Experientia.

[23]  J. Závada.  Pseudotypes of vesicular stomatitis virus with the coat of murine leukaemia and of avian myeloblastosis viruses. , 1972, The Journal of general virology.

[24]  V. Georgiev.  Virology , 1955, Nature.