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G3P2 rotaviruses causing diarrhoeal disease in neonates differ in VP4, VP7 and NSP4 sequence from G3P2 strains
C D Kirkwood1, B S Coulson, R F Bishop
1Department of Gastroenterology, Royal Children's Hospital, Parkville, Victoria, Australia.
Insights
Human G3P2 rotavirus strains were analyzed for genetic differences linked to asymptomatic versus symptomatic infections in infants. Specific amino acid variations in VP4, VP7, and NSP4 proteins correlate with disease severity, suggesting a genetic basis for rotavirus virulence.
Area of Science:
- Virology
- Epidemiology
- Genetics
Background:
- Longitudinal studies in Melbourne, Australia identified human G3P2 rotavirus strains causing asymptomatic and symptomatic infections in infants.
- Eleven asymptomatic strains (AS) from 1974-1984 and five symptomatic strains (S) from 1980-1986 were analyzed.
Purpose of the Study:
- To investigate the genetic basis for differences in virulence between asymptomatic and symptomatic human G3P2 rotavirus strains.
- To compare nucleotide and amino acid sequences of key viral proteins between AS and S strains.
Main Methods:
- Whole nucleotide sequencing of genes encoding VP4, VP7, NSP4, and VP6 for representative AS and S strains.
- Analysis of nucleotide and deduced amino acid sequences, focusing on neutralization epitope regions and specific amino acid residues.
Main Results:
- Extensive conservation of nucleotide and amino acid sequences in VP4 and VP7 neutralization epitopes (regions C and F) across all strains.
- Minor variations observed in VP7 epitope regions A and B over the 12-year study period.
- Specific amino acid differences identified in VP4, VP7, and NSP4 proteins between AS and S strains, correlating with clinical symptoms.
Conclusions:
- Observed amino acid differences in virulence-associated proteins (VP4, VP7, NSP4) provide insights into the genetic determinants of human rotavirus virulence.
- These findings suggest a molecular basis for the varying clinical presentations of rotavirus infections in infants.
Abstract:
During longitudinal epidemiological studies of rotavirus infections in children in Melbourne, Australia human G3P2 rotavirus strains causing asymptomatic or symptomatic infections have been identified. Eleven strains (AS strains) associated with asymptomatic infection of newborn babies from 1974-1984, and five strains (S strains) associated with symptomatic infection of newborn babies (4) or a 22 week old infant (1) during 1980-1986 were studied. The entire nucleotide sequences of genes coding for VP4, VP7, NSP4 and VP6 were derived for representative AS and S strains. The nucleotide sequences of neutralization epitope regions present on the outer capsid proteins VP4 and VP7 (regions C and F) showed extensive conservation of nucleotide and deduced amino acid sequence in all strains. Minor variations were observed over the 12 year period in VP7 epitope regions A and B in some strains. Specific conserved amino acids differences between the asymptomatic and symptomatic strains were observed in the genes encoding VP4 at aa133 and 303 (asparagine or threonine) and 380 (serine or isoleucine), VP7 at aa27 (threonine or isoleucine), aa29 (isoleucine or threonine), aa42 (valine or alanine) and aa238 (asparagine or aspartic acid/serine) and NSP4 at aa135 (isoleucine or valine). No amino acid changes were identified in gene 6. The observed amino acid differences occurred in proteins that have been implicated in virulence, and correlate with differences in clinical symptoms of infants infected with these strains. These results permit speculation about the genetic basis for virulence of human strains.