Sequence analysis of an isolate from a fatal human infection of Australian bat lyssavirus

Australian bat lyssavirus (ABLV), which occurs in pteropid and insectivorous bat populations, causes a rabies-like encephalitis in infected humans. We report the first complete sequence of an ABLV isolate obtained from a human who developed symptoms 27 months after being bitten by an infected flying fox. This isolate is the smallest lyssavirus to be sequenced, with a size of 11,918 nucleotides. Analyses of previously unsequenced regions and the complete genome confirm its close relationship with classical rabies viruses. In addition, a leucine zipper-like motif, not present in the other lyssaviruses, was found in the conserved domain I of the polymerase protein. This is the first report of a lyssavirus to vary in an 11-nucleotide, strictly conserved, complementary terminal sequence. This region is thought to encode important cis-acting regulatory signals; ABLV variation indicates a greater degree of flexibility than was thought for lyssaviruses in this region. A comparison of the pteropid and insectivorous isolates of ABLV indicates considerable differences between the two viruses. If the divergence of the two occurred on the Australian mainland, ABLV may have been endemic to Australia well before European colonisation.