Spl574 MLV (murine leukemia virus) is a variant of Moloney ecotropic MLV (MoMLV) that is cytopathic in Mus dunni cells and restricted by other mouse cells. Its host range and cytopathicity are due to a mutation, S82F, at a site critical for binding to the CAT-1 receptor. To identify residues that affect affinity for receptor variants, virus with S82F was passed in restrictive cells. The env genes of the adapted viruses contained 18 novel mutations, including one, E114G, present in 6 of 30 sequenced envs. MoMLV-E114G efficiently infected all mouse cells as well as ecotropic MLV resistant Chinese hamster cells. Virus with E114G and S82F induced large multinucleated syncytia in NIH 3T3 and SC-1 cells as well as M. dunni cells. Inoculation of Mo-S82F,E114G into mice produced lymphomas typical of MoMLV. Residues at env position 114 are thus important determinants of host range, and E114G suppresses host range restriction due to S82F, but does not affect S82F-governed cytopathicity.
Bibliographical noteFunding Information:
This research was supported by the Intramural Research Program of the NIAID, NIH . We thank Esther Shaffer and Qingping Liu for expert technical assistance, Alicia Buckler-White and Ronald Plishka for sequencing, Michael A. Dolan of the Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID for assistance with figure preparation, and the following members of the Division of Veterinary Resources, Office of Research Services, NIH, for pathological evaluation: Lauren Brinster, Mark Bryant, Michael Eckhaus, Randy Elkins, Victoria Hoffmann, and Matthew Starost.
- Cat-1 retrovirus receptor
- Mouse ecotropic gammaretrovirus
- Receptor binding domain
- Retrovirus entry
- Retrovirus host range
- Virus-induced syncytia