Arch Virol (1987) 93:111-121 Archives of Virology © by Springer-Verlag 1987 Marked Sequence Variation Between Segment 4 Genes of Human RV-5 and Simian SA 11 Rotaviruses By P. KANTHARIDIS, M.L. DYALL-SMITH, and I. H. HOLMES School of Microbiology, University of Melbourne, Parkvitle, Victoria, Australia With 3 Figures Accepted July 9, t986 Summary The complete nucleotide sequence of dsl~NA gene segment 4 of a human serotypc 2 rotavirus, RV-5, was determined by sequencing overlapp- ing cloned DNA copies of the gene. Segment 4 is 2359 base pairs in length and contains a single long open reading frame of 2325 bases capable of coding for a protein of 775 amino acids, with 5' and 3' non coding regions of 9 and 25 nucleotides respectively. Comparison with SA 11 segment 4 sequence reveals a moderately conserved trypsin cut site and an overall amino acid homology of 69.8 percent. One localized region of 126 amino acids is only 37.8 percent homologous. Localized frame shifts account for some of this variation, but at the nucleotide level tile segment 4 sequences show more variability than other rotavirus genes that have been studied so far. Introduction I~otavirus are an important cause of diarrhoeal disease in many mamma- lian species (18, 23, 40), and are responsible for a large number of infant deaths in developing countries every year (35). It is therefore not suprising that a great deal of current works is beginning to focus on research that may eventually lead to the production of an effective rotaviral vaccine (18, 25, 38). At least tire structural polypeptides have been identified as components of the double layered protein capsid that encloses the RNA genome of rota- viruses (17, 31). One of these, the major outer-shell glycoprotein, has been