Lineage diversification and recombination in type-4 human astroviruses

Human astroviruses (HAstVs) are important enteric pathogens and can be classified genetically and antigenically into eight types. During surveillance of HAstVs in Italy, type-4 HAstVs were detected only sporadically and found to cluster into two distinct genetic groups. Upon sequence analysis of the 3' end of the polymerase gene (ORF1b) and of the full-length ORF2, the 2008 type-4 HAstV strains were characterised as a novel ORF2 genetic lineage, designated as 4c. The 2008 type-4 HAstVs also shared the ORF1b gene with similar HAstV-4c strains detected globally, thus displaying a conserved ORF1b/ORF2 asset. By interrogation of the databases, this novel lineage 4c accounted for 60.8% of the type-4 strains identified worldwide and the vast majority of recent type-4 HAstVs. The 2002 type-4 HAstVs displayed a type-4b ORF2, whereas in the ORF1b they resembled type-1 HAstVs. This inconsistency suggests a possible recombinant origin, with the RNA switch taking place upstream the ORF1b/ORF2 junction region. Also, recombination likely played a role in the diversification of the ORF2 of the three type-4 lineages. Multi-target analysis is required for appropriate characterisation and identification of recombinant HAstVs.