The present invention provides compositions and methods for the construction of nucleic acids comprising all or portion of a viral genome. Nucleic acid molecules of the invention may be constructed to contain multiple recombination and/or topoisomerase recognition sites. The compositions include vectors having multiple recombination sites with unique specificity that contain all or a portion of a viral genome. The methods permit the insertion of a sequence of interest into a viral genome using recombinational and/or topoisomerase-mediated cloning. The present invention also provides methods of constructing recombinant virus, methods of expressing polypeptides, and methods of expressing fusion polypeptides.