SEQUENCE OF THE FOURTH ROTAVIRUS GENE AND ITS ROLE IN VIRULENCE

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The fourth gene of rotavirus strains recovered from outbreaks of asymptomatic infection in newborn nurseries exhibits a marked conservation of sequence. Similarly, the fourth gene of virulent rotaviruses exhibits conservation of sequence but this conserved sequence differs from that of the asymptomatic strains. This gene 4 sequence dimorphism was studied by sequence analysis of the region of the fourth gene that codes for the VP8 protein, downstream cleavage sites and the N terminus of VP5. The human rotaviruses exhibit many similarities in this region of their genome, including identical N-terminal amino acid sequences, conservation of arginine at the two trypsin cleavage sites and the position of a cysteine residue. Alignment of amino acid sequences of asymptomatic and virulent human rotavirus strains indicates a high degree of homology (96% or more) among the asymptomatic viruses (serotypes 1, 2, 3 and 4), while homology between asymptomatic strains and virulent viruses is considerably less (68-72%). A high degree of conservation of amino acid sequence (92-97%) is also observed among 3 of the virulent strains (serotypes 1, 3 and 4). At 48 positions in the protein sequence of VP8, the cleavage region and the N terminus of VP5 an amino acid is conserved among asymptomatic rotaviruses, while a different amino acid is conserved among virulent rotaviruses. Notably, three of these differences are located within the short 6 amino acid cleavage region between VP8 and VP5. It is possible that some or all of this sequence dimorphism may be responsible for the difference in virulence between these two groups of human rotaviruses.