RNA SEQUENCE OF ASTROVIRUS - DISTINCTIVE GENOMIC ORGANIZATION AND A PUTATIVE RETROVIRUS-LIKE RIBOSOMAL FRAMESHIFTING SIGNAL THAT DIRECTS THE VIRAL REPLICASE SYNTHESIS

The genomic RNA of human astrovirus was sequenced and found to contain 6797 nt organized into three open reading frames (1a, 1b, and 2). A p otential ribosomal frameshift site identified in the overlap region of open reading frames 1a and 1b consists of a ''shifty'' heptanucleotid e and an RNA stem-loop structure that closely resemble those at the ga g-pro junction of some retroviruses. This translation frameshift may r esult in the suppression of in-frame amber termination at the end of o pen reading frame 1a and the synthesis of a nonstructural, fusion poly protein that contains the putative protease and RNA-dependent RNA poly merase. Comparative sequence analysis indicated that the protease and polymerase of astrovirus are only distantly related to the respective enzymes of other positive-strand RNA viruses. The astrovirus polyprote in lacks the RNA helicase domain typical of other positive-strand RNA viruses of similar genome size. The genomic organization and expressio n strategy of astrovirus, with the protease and the polymerase brought together by predicted frameshift, most closely resembled those of pla nt luteoviruses. Specific features of the sequence and genomic organiz ation support the classification of astroviruses as an additional fami ly of positive-strand RNA viruses, designated Astroviridae.