Role of receptor polymorphism and glycosylation in syncytium induction and host range variation of ecotropic mouse gammaretroviruses

Yuhe Yan,Tiyun Wu,Yong T Jung,Christine A Kozak

doi:10.1186/1742-4690-5-2

Abstract

BackgroundWe previously identified unusual variants of Moloney and Friend ecotropic mouse gammaretroviruses that have altered host range and are cytopathic in cells of the wild mouse species Mus dunni. Cytopathicity was attributed to different amino acid substitutions at the same critical env residue involved in receptor interaction: S82F in the Moloney variant Spl574, and S84A in the Friend mouse leukemia virus F-S MLV. Because M. dunni cells carry a variant CAT-1 cell surface virus receptor (dCAT-1), we examined the role of this receptor variant in cytopathicity and host range.ResultsWe expressed dCAT-1 or mCAT-1 of NIH 3T3 origin in cells that are not normally infectible with ecotropic MLVs and evaluated the transfectants for susceptibility to virus infection and to virus-induced syncytium formation. The dCAT-1 transfectants, but not the mCAT-1 transfectants, were susceptible to virus-induced cytopathicity, and this cytopathic response was accompanied by the accumulation of unintegrated viral DNA. The dCAT-1 transfectants, however, did not also reproduce the relative resistance of M. dunni cells to Moloney MLV, and the mCAT-1 transfectants did not show the relative resistance of NIH 3T3 cells to Spl574. Western analysis, use of glycosylation inhibitors and mutagenesis to remove receptor glycosylation sites identified a possible role for cell-specific glycosylation in the modulation of virus entry.ConclusionVirus entry and virus-induced syncytium formation using the CAT-1 receptor are mediated by a small number of critical amino acid residues in receptor and virus Env. Virus entry is modulated by glycosylation of cellular proteins, and this effect is cell and virus-specific.

Highlights

We previously identified unusual variants of Moloney and Friend ecotropic mouse gammaretroviruses that have altered host range and are cytopathic in cells of the wild mouse species Mus dunni
Syncytium formation in cells expressing mCAT-1 or dCAT1 HA-tagged mCAT-1 and dCAT-1 clones were transfected into three cell lines that are not naturally susceptible to infection by ecotropic mouse gammaretroviruses: MA139
These stable transfectants of MA139, Tb-1-Lu and MDCK cells were infected with a panel of ecotropic gammaretroviruses including two, Spl574 and F-S mouse leukemia virus (MLV) that induce multinucleated syncytia in M. dunni cells but not in other mouse cell lines

Summary

Introduction

We previously identified unusual variants of Moloney and Friend ecotropic mouse gammaretroviruses that have altered host range and are cytopathic in cells of the wild mouse species Mus dunni. In previous studies we identified two unusual ecotropic mouse leukemia virus (MLV) variants [1,2] Both of these viruses have altered host range, both are cytopathic, and both have amino acid substitutions at the (page number not for citation purposes). Spl574 is a Moloney MLV (MoMLV) variant with the substitution S82F, and F-S MLV is a Friend MLV (FrMLV) variant with the substitution S84A Both viruses cause the formation of large multinucleated syncytia on cells derived from the wild mouse species M. dunni two days after infection, and syncytium formation is accompanied by the accumulation of large amounts of unintegrated viral DNA [2]. F-S MLV shows no unusual pattern of infectivity in mouse cells, but is capable of infecting hamster cells that are normally resistant to ecotropic MLVs

Results

Discussion

Conclusion