Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2775717 | Experimental and Molecular Pathology | 2008 | 13 Pages |
Abstract
Removal of the R peptide (residues 617-632) from the Moloney murine leukemia virus (MoMuLV) envelope protein (Env) cytoplasmic tail potentiates fusion. We examined the role of the membrane-proximal cytoplasmic domain (598-616) of the MoMuLV Env in the Env-mediated membrane fusion and incorporation. The Env truncated at 616 exhibits maximum fusogenicity in cell-to-cell fusion assay. By comparison, full tail Env (632) and the Env truncated to residue 601 mediated fusion at 40%. The Envs truncated to residues 598 or 595 are not fusogenic. Progressive cytoplasmic tail truncation correlated with decreased Env incorporation into virions. Substitution of the domain 598-616 with an amphiphilic α-helix from melittin results in maximally fusogenic Envs that efficiently incorporated into transduction competent virions. However, substitution of the domain 598-616 with random or hydrophilic sequences caused loss of the Env fusogenicity and titer while retaining incorporation. Further, a secondary structure prediction analysis of 27 unrelated Env cytoplasmic tails indicates a common (23/27) propensity for an amphiphilic α-helical domain at immediate proximity to the viral membrane. These results support the suggestion that viral fusion is enhanced by a membrane-proximal cytoplasmic amphiphilic α-helix in Env tail. The model of its action is proposed.
Keywords
EIAVMoMuLVMuLVSV5Viral envelope proteinMPMVd10BLVHuman T cell leukemia virusHRSVVSVHTLVGLASNVRSVinfMMTVFIVhemagglutininHepatitis C virusVesicular stomatitis virusEquine infectious anemia virusMurine mammary tumor virusRous sarcoma virusSimian virusMoloney murine leukemia virusMurine leukemia virusBovine leukemia virusavian leukosis virusMason-Pfizer monkey virushuman immunodeficiency virusHIVFeline immunodeficiency virusSpleen necrosis virusParainfluenza virus
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Authors
Yanina Rozenberg-Adler, John Conner, Hector Aguilar-Carreno, Samitabh Chakraborti, Dimiter S. Dimitrov, W. French Anderson,