Norovirus Recombination in ORF1/ORF2 Overlap

Abstract

Norovirus (NoV) genogroups I and II (GI and GII) are now recognized as the predominant worldwide cause of outbreaks of acute gastroenteritis in humans. Three recombinant NoV GII isolates were identified and characterized, 2 of which are unrelated to any previously published recombinant NoV. Using data from the current study, published sequences, database searches, and molecular techniques, we identified 23 recombinant NoV GII and 1 recombinant NoV GI isolates. Analysis of the genetic relationships among the recombinant NoV GII isolates identified 9 independent recombinant sequences; the other 14 strains were close relatives. Two of the 9 independent recombinant NoV were closely related to other recombinants only in the polymerase region, and in a similar fashion 1 recombinant NoV was closely related to another only in the capsid region. Breakpoint analysis of recombinant NoV showed that recombination occurred in the open reading frame (ORF)1/ORF2 overlap. We provide evidence to support the theory of the role of subgenomic RNA promoters as recombination hotspots and describe a simple mechanism of how recombination might occur in NoV.

Feline calicivirus

“…In addition, the high prevalence of FCV in such colonies provides an ideal environment for mixed infections. As a result recombination events between strains, similar to those reported for other caliciviruses [7,46,50,73], have been identified in such colonies, and provide a further mechanism for the diversification of viruses [16]. Whether these evolutionary events are associated with the selection of more virulent, faster replicating viral variants remains to be determined.…”

Detection of Enteric Viruses in Fecal Specimens from Nonbacterial Foodborne Gastroenteritis Outbreaks in Tokyo, Japan between 1966 and 1983

“…ORF1 encodes nonstructural proteins, while ORF2 and ORF3 encode the structural proteins VP1 and VP2, respectively. Recombination at the ORF1-ORF2 junction has been reported (12). Amino acid substitutions in the P2 domain, located within the VP1 of NoVs, have also been reported, especially in NoV GII.4 (13).…”

Quasispecies dynamics and molecular evolution of human norovirus capsid P region during chronic infection

“…While Lindesmith and coworkers have identified a recombination breakpoint at residue 265 located near the P1-1/P2 domain interface of NoV GII.4 strains (Lindesmith et al, 2008), this recombination break point was not found in this study. The absence of detected recombinants might be due to the fact that we did not have access to ORF1/ORF2 overlap sequences, previously found associated with NoV recombination break points (Bull et al, 2005(Bull et al, , 2007Phan et al, 2007). Thus, we cannot rule out that recombination occurred at the ORF1/ORF2 junction.…”

“…Since RNA recombination is believed to be one of the major driving forces in viral evolution (Worobey & Holmes, 1999), including NoV (Bull et al, 2005(Bull et al, , 2007Phan et al, 2007), we searched the 134 full-length (P1-1 and P2 capsid domains) NoV capsid nudeotide sequences for recombination events. The sequences were first aligned using CLUSTAL W-multialign with default settings on the Mobyle portal (Pasteur Institute), and then analysed by the RDP2 software to search for possible recombinants using different conventional recombination detection methods such as GENECONV, SIMPLOT, BOOTSCAN, MAXIMUM x 2 and CHIMAERA (Martin et al, 2005).…”

“…Since RNA recombination is believed to be one of the major driving forces in viral evolution, (Worobey & Holmes, 1999) including NoV (Bull et al, 2005(Bull et al, , 2007Phan et al, 2007), we searched the 134 full-length NoV capsid sequences (597 nt from the P1-1and P2 capsid domains) for recombination events. Some possible recombination events were located (e.g.…”