Human astrovirus C-terminal nsP1a protein is involved in RNA replication

Human astrovirus nonstructural C-terminal nsP1a protein, which contains a hypervariable region (HVR) and colocalizes with the endoplasmic reticulum and viral RNA, has been suggested to be involved in the RNA replication process. Four viruses differing only in their C-terminal nsP1a protein, corresponding to HVR-derived genotypes IV, V, VI, and XII, were all able to replicate in CaCo-2 cells but displayed differences in their RNA replication and growth properties. Two overall patterns of replication were observed: types IV and V on one side, and types VI and XII on the other. The main detected differences were on the levels of antigenomic and subgenomic RNAs, being the latter significantly higher in types IV and V. Accordingly, quantification of viral RNA load in feces from children with gastroenteritis showed that HVR-derived genotypes IV and V occur in significantly higher numbers. In consequence, it may be concluded that the variability of the C-terminal nsP1a gene affects the virus replication phenotype.