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Replication-Competent Hybrids between Murine Leukemia Virus and Foamy Virus

Evelina Shikova-Lekova,^1, Dirk Lindemann,^1,2 Thomas Pietschmann,^2, Thomas Juretzek,¹ Wolfram Rudolph,¹ Ottmar Herchenröder,¹ Hans R. Gelderblom,³ and Axel Rethwilm^1,2*

Institut für Virologie, Medizinische Fakultät, Technische Universität Dresden, Dresden,¹ Institut für Virologie und Immunbiologie, Universität Würzburg, Würzburg,² Robert Koch-Institut, Berlin, Germany³

Received 2 December 2002/ Accepted 2 April 2003

Replication-competent chimeric retroviruses constructed of members of the two subfamilies of Retroviridae, orthoretroviruses and spumaretroviruses, specifically murine leukemia viruses (MuLV) bearing hybrid MuLV-foamy virus (FV) envelope (env) genes, were characterized. All viruses had the cytoplasmic tail of the MuLV transmembrane protein. In ESL-1, a truncated MuLV leader peptide (LP) was fused to the complete extracellular portion of FV Env, and ESL-2 to -4 contained the complete MuLV-LP followed by N-terminally truncated FV Env decreasing in size. ESL-1 to -4 had an extended host cell range compared to MuLV, induced a cytopathology reminiscent of FVs, and exhibited an ultrastructure that combined the features of the condensed core of MuLV with the prominent surface knobs of FVs. Replication of ESL-2 to -4 resulted in the acquisition of a stop codon at the N terminus of the chimeric Env proteins. This mutation rendered the MuLV-LP nonfunctional and indicated that the truncated FV-LP was sufficient to direct Env synthesis into the secretory pathway. Compared to the parental viruses, the chimeras replicated with only moderate cell-free titers.

Permanent address: Department of Oncovirology, Institute of Experimental Pathology and Parasitology, Bulgarian Academy of Sciences, Sofia, Bulgaria.

Present address: Institut für Molekulare Virologie, Universität Heidelberg, Germany.

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