Generation of novel syncytium-inducing and host range variants of ecotropic moloney murine leukemia virus in Mus spicilegus.
Mus spicilegus is an Eastern European wild mouse species that has previously been reported to harbor an unusual infectious ecotropic murine leukemia virus (MLV) and proviral envelope genes of a novel MLV subgroup. In the present study, M. spicilegus neonates were inoculated with Moloney ecotropic MLV (MoMLV). All 17 inoculated mice produced infectious ecotropic virus after 8 to 14 weeks, and two unusual phenotypes distinguished the isolates from MoMLV. First, most of the M. spicilegus isolates grew to equal titers on M. dunni and SC-1 cells, although MoMLV does not efficiently infect M. dunni cells. The deduced amino acid sequence of a representative clone differed from MoMLV by insertion of two serine residues within the VRA of SUenv. Modification of a molecular clone of MoMLV by the addition of these serines produced a virus that grows to high titer in M. dunni cells, establishing a role for these two serine residues in host range. A second unusual phenotype was found in only one of the M. spicilegus isolates, Spl574. Spl574 produces large syncytia of multinucleated giant cells in M. dunni cells, but its replication is restricted in other mouse cell lines. Sequencing and mutagenesis demonstrated that syncytium formation could be attributed to a single amino acid substitution within VRA, S82F. Thus, viruses with altered growth properties are selected during growth in M. spicilegus. The mutations associated with the host range and syncytium-inducing variants map to a key region of VRA known to govern interactions with the cell surface receptor, suggesting that the associated phenotypes may result from altered interactions with the unusual ecotropic virus mCAT1 receptor carried by M. dunni.
Jung
Yong Tae
YT
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460, USA.
Kozak
Christine A
CA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D015726:Giant Cells / Q000502:physiology*; D007942:Leukemia, Experimental / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D009115:Muridae / Q000821:virology*; D016297:Mutagenesis, Site-Directed; D011991:Receptors, Virus / Q000378:metabolism; D012192:Retroviridae Infections / Q000821:virology; D017422:Sequence Analysis, DNA; D014412:Tumor Virus Infections / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
D011991:Receptors, Virus; D014759:Viral Envelope Proteins