ORIGINAL ARTICLE Whole-genome analysis of a human rabies virus from Sri Lanka Takashi Matsumoto • Kamruddin Ahmed • Omala Wimalaratne • Kentaro Yamada • Susilakanthi Nanayakkara • Devika Perera • Dushantha Karunanayake • Akira Nishizono Received: 14 June 2010 / Accepted: 21 December 2010 / Published online: 6 February 2011 Ó Springer-Verlag 2011 Abstract The complete genome sequence of a human rabies virus, strain H-08-1320, from Sri Lanka was deter- mined and compared with other rabies viruses. The size of the genome was 11,926 nt, and it was composed of a 58-nucleotide 3 0 leader, five protein genes – N (1353 nt), P (894 nt), M (609 nt), G (1575 nt), and L (6387 nt) – and a 70-nt 5 0 trailer. The intergenic region G–L contained 515 nt. The sizes of the nucleoprotein, phosphoprotein, matrix- protein, glycoprotein and large-protein was 450, 296, 202, 524 and 2,128 residues, respectively. The phosphoprotein and large protein were one amino acid shorter and longer, respectively, than those of most rabies viruses. The gly- coprotein of H-08-1320 had a unique amino acid substi- tution at antigenic site I. Whole-genome phylogenetic analysis showed that strain H-08-1320 formed an inde- pendent lineage and did not cluster with rabies viruses from other countries. Introduction Human rabies is a universally fatal zoonotic disease once clinical signs develop. Except in a few countries, it is present globally. Each year, an estimated 55,000 people, mainly in Asia and Africa, die from rabies. The actual number may be significantly higher than this figure. Sri Lanka is not an exception; it is severely affected by rabies. Rabies virus belongs to the genus Lyssavirus of the family Rhabdoviridae. The genome is a single-stranded, negative-sense RNA of approximately 12 kb that encodes five structural proteins in the order nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and RNA-dependent RNA polymerase (L). These are separated by intergenic regions of variable length. The N protein forms nucleoprotein core with the P and L proteins and regulates RNA transcription. The P protein is capable of oligomerization or binding to the N-RNA template [20]. This protein interacts with the cytoplasmic dynein light chain protein, which helps the axoplasmic transport of viral nucleocapsid [49]. The P protein also acts as a chaperone of soluble nascent N protein [20]. At least in fixed rabies virus strains, both the P and N proteins have anti-interferon activities [26, 34]. The M protein is involved in the down- regulation of viral RNA transcription, condensation of helical nucleocapsid cores into tight coils, association with membrane bilayers, and cytopathogenesis of infected cells [17, 18, 28, 35, 39]. The G protein plays an important role in the attachment of rabies virus to the host-cell surface, pathogenicity [40] and neurovirulence [54]. The L protein is the polymerase of the nucleoprotein core and is involved in viral RNA transcription and replication [43]. It is surprising that, currently, only a few complete genome sequences for street rabies viruses are available. As a result, the phylogeny and dynamics of this virus have Electronic supplementary material The online version of this article (doi:10.1007/s00705-010-0905-8) contains supplementary material, which is available to authorized users. T. Matsumoto Á A. Nishizono Department of Microbiology, Faculty of Medicine, Oita University, Yufu, Japan K. Ahmed (&) Á K. Yamada Research Promotion Project, Oita University, Yufu, Oita 879-5593, Japan e-mail: ahmed@med.oita-u.ac.jp O. Wimalaratne Á S. Nanayakkara Á D. Perera Á D. Karunanayake Rabies Laboratory, Medical Research Institute, Colombo, Sri Lanka 123 Arch Virol (2011) 156:659–669 DOI 10.1007/s00705-010-0905-8