title: Endophilins interact with Moloney murine leukemia virus Gag and modulate virion production.
abstract: BACKGROUND
  The retroviral Gag protein is the central player in the process of virion assembly at the plasma membrane, and is sufficient to induce the formation and release of virus-like particles. Recent evidence suggests that Gag may co-opt the host cell's endocytic machinery to facilitate retroviral assembly and release.
  
  
  RESULTS
  A search for novel partners interacting with the Gag protein of the Moloney murine leukemia virus (Mo-MuLV) via the yeast two-hybrid protein-protein interaction assay resulted in the identification of endophilin 2, a component of the machinery involved in clathrin-mediated endocytosis. We demonstrate that endophilin interacts with the matrix or MA domain of the Gag protein of Mo-MuLV, but not of human immunodeficiency virus, HIV. Both exogenously expressed and endogenous endophilin are incorporated into Mo-MuLV viral particles. Titration experiments suggest that the binding sites for inclusion of endophilin into viral particles are limited and saturable. Knock-down of endophilin with small interfering RNA (siRNA) had no effect on virion production, but overexpression of endophilin and, to a lesser extent, of several fragments of the protein, result in inhibition of Mo-MuLV virion production, but not of HIV virion production.
  
  
  CONCLUSIONS
  This study shows that endophilins interact with Mo-MuLV Gag and affect virion production. The findings imply that endophilin is another component of the large complex that is hijacked by retroviruses to promote virion production.
authors.affiliation: Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Margaret Q
authors.initials: MQ
authors.lastname: Wang
authors.forename: Wankee
authors.initials: W
authors.lastname: Kim
authors.forename: Guangxia
authors.initials: G
authors.lastname: Gao
authors.forename: Ted A
authors.initials: TA
authors.lastname: Torrey
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Goff
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics; D015683:Gene Products, gag / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007668:Kidney / Q000166:cytology / Q000196:embryology; D008979:Moloney murine leukemia virus / Q000235:genetics*; D010446:Peptide Fragments / Q000096:biosynthesis; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D013045:Species Specificity; D014162:Transfection; D022161:Transport Vesicles / Q000737:chemistry / Q000235:genetics; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins / Q000378:metabolism; D014771:Virion / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015683:Gene Products, gag; D010446:Peptide Fragments; C429293:SH3GLB1 protein, human; D033921:Vesicular Transport Proteins; D010447:Peptide Hydrolases