Mouse tetherin enhances moloney murine leukemia virus-induced syncytium formation

Tetherin (also referred to as BST-2 or CD317) is an antiviral cellular restriction factor that inhibits the release of many enveloped viruses. It is a 30-36 kDa type II transmembrane protein, expression of which is induced by type I interferon. Mouse tetherin inhibits nascent cell-free particle release. However, it is unclear whether mouse tetherin restricts cell-to-cell spread of moloney murine leukemia virus (Mo-MLV) or whether is the mouse tetherin involved in syncytium formation. To examine cell-to-cell spread and syncytium formation of Mo-MLV in the presence or absence of mouse tetherin, R peptide (the cytoplasmic tail of the transmembrane protein (TM); 16 amino acids) truncated Env expressing vector was constructed. It contained enhanced green fluorescent protein (EGFP) in the proline rich region (PRR) of Env. This R(-)Env full-length molecular clone could rule out virus-cell transmission due to the slightly reduced R(-)Env protein incorporation into the viral particles. When NIH3T3 cells stably expressing mouse tetherin were transfected with R(-)Env full-length molecular clone, syncytium formation was significantly enhanced in the tetherin-expressing cells. These data suggest that tetherin-mediated retention of R-defective virions on the cell surface could enhance syncytium formation. In addition, we found that the R(-)Env full-length molecular clone containing EGFP in the PRR of Env to be a useful tool allowing fast and convenient detection of syncytia by fluorescence microscopy.