Mechanisms underlying glycosylation-mediated loss of ecotropic receptor function in murine MDTF cells and implications for receptor evolution

Author:

Yoshii Hiroaki12,Kamiyama Haruka2,Amanuma Hiroshi3,Oishi Kazunori41,Yamamoto Naoki52,Kubo Yoshinao2

Affiliation:

1. Department of Preventive and Therapeutic Research for Infectious Diseases, Course of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

2. Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan

3. Molecular Cell Science Laboratory, RIKEN, Saitama, Japan

4. International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

5. AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan

Abstract

A Mus dunni tail fibroblast (MDTF) cell line is highly resistant to infection by ecotropic Moloney murine leukemia virus (Mo-MLV). The cationic amino acid transporter type 1 (CAT1) paralogues of murine NIH 3T3 and MDTF cells (mCAT1 and dCAT1, respectively) contain two conserved N-linked glycosylation sites in the third extracellular loop (ECL3, the putative Mo-MLV binding site). Glycosylation of dCAT1 inhibits Mo-MLV infection, but that of mCAT1 does not. Compared with mCAT1, dCAT1 possesses an Ile-to-Val substitution at position 214 and a Gly insertion at position 236 in the ECL3. To determine the residues responsible for the loss of dCAT1 receptor function, mutants of mCAT1 were constructed. The mCAT1/insG receptor (with a Gly residue inserted at mCAT1 position 236) had greatly reduced Mo-MLV receptor function compared with mCAT1. Treatment of mCAT1/insG-expressing cells with tunicamycin, an N-linked glycosylation inhibitor, increased the transduction titre. In addition, the reduced susceptibility to Mo-MLV observed with mCAT1/insG-expressing cells correlated with impaired binding of Mo-MLV. These results show that a single amino acid insertion confers mCAT1 receptor properties on dCAT1 and provide an important insight into the co-evolution of virus–host interactions.

Publisher

Microbiology Society

Subject

Virology

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