ALTERED TROPISM OF AN OVINE ADENOVIRUS CARRYING THE FIBER PROTEIN CELL-BINDING DOMAIN OF HUMAN ADENOVIRUS TYPE-5

Ovine adenovirus OAV287 (OAV) is phylogenetically and serotypically di stinct from human Ad5. OAV grows productively in CSL503 foetal ovine l ung cells and abortively infects several human cell lines. OAV has a u nique fiber and a penton protein that lacks a recognisable integrin-bi nding motif. It is not known whether a secondary receptor is required for infection. A hybrid virus was constructed in which the cell bindin g domain on the OAV fiber protein was exchanged for the equivalent reg ion from human adenovirus type 5. The hybrid OAV grew to titres that w ere 1 to 2 log(10) lower than wild-type OAV in permissive ovine cells. Human Ad5 also infected CSL503 cells but failed to compete with OAV f or receptor binding sites on those cells. However, the hybrid virus di d compete with Ad5, consistent with its use of the Ad primary receptor . The hybrid virus was also neutralised by Ad5 antiserum whereas OAV w as not. Human 293 kidney and LNCaP prostate cell lines that were not d electably infected by OAV were infected by the hybrid virus and other human prostate and breast cancer cell lines showed greatly enhanced in fectivity. Thus, modification of the fiber cell binding domain was suf ficient to profoundly alter the tropism of OAV, suggesting that the in teraction between the primary receptor and the virus particle is the m ajor factor controlling virus entry during infection. (C) 1998 Academi c Press.