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Development of a Novel Surrogate Virus for Human T-Cell Leukemia Virus Type 1: Inhibition of Infection by Osteoprotegerin

Kazu Okuma,^* Kevin P. Dalton, Linda Buonocore, Elizabeth Ramsburg, and John K. Rose^*

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520

Received 16 January 2003/ Accepted 3 May 2003

To develop a high-titer surrogate virus for human T-cell leukemia virus type 1 (HTLV-1), we generated recombinant vesicular stomatitis viruses (VSVs) in which the gene encoding the single transmembrane glycoprotein (G) was deleted. Genes encoding HTLV-1 envelope glycoproteins (HTEnv) or HTEnvG hybrid proteins were then inserted into either of two different sites in the VSV genome. The viruses also encoded a green fluorescent protein. With this surrogate virus, we found that a soluble protein, osteoprotegerin (OPG), or an OPG/Fc chimeric protein inhibited the infection of various cell lines. Our experiments indicate that this inhibition resulted from binding of heparan sulfate by OPG.

Present address: School of Animal and Microbial Sciences, University of Reading, Reading RG6 6AJ, United Kingdom.

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