SEQUENCE CONSERVATION WITHIN NEUTRALIZATION EPITOPE REGIONS OF VP7 AND VP4 PROTEINS OF HUMAN SEROTYPE-G4 ROTAVIRUS ISOLATES

Serotype G 4 rotavirus isolates causing four separate epidemics of sev ere diarrhoea in young children in Melbourne, Australia (from 1974-199 0) were investigated for sequence variation in genes encoding the oute r capsid proteins, VP 4 and VP 7. Complementary DNA of the gene encodi ng the major outer capsid neutralization antigen, VP 7, of eighteen is olates was synthesized and amplified by coupled reverse transcription and polymerase chain reaction. Direct sequencing methods were used to derive the deduced amino acid sequences of the immunodominant A, B, an d C neutralization epitope regions of the protein. Limited variation w as observed among all isolates. A threonine to asparagine change in re gion A, at amino acid 96, was associated with altered binding of serot ype G 4-specific neutralizing monoclonal antibodies. The VP8 region o f the outer capsid protein VP4 (containing the proposed serotype-speci fic neutralization epitopes) was investigated in eight isolates. This region was found to be highly conserved both within Melbourne isolates and in relation to the standard strains Wa, P, and VA 70. The charact eristic periodicity of occurrence of serotype G 4 isolates causing sev ere diarrhoea in Melbourne children is unlikely to be due to changes i n neutralization epitopes located on the outer capsid proteins, VP 7 o r VP 4.