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Rearrangements of Rotavirus Genomic Segment 11 Are Generated during Acute Infection of Immunocompetent Children and Do Not Occur at Random

Nathalie Schnepf ,^1,2,, Claire Deback,^1,, Axelle Dehee,^1,2 Elyanne Gault,¹ Nathalie Parez,¹ and Antoine Garbarg-Chenon^1,2*

Université Pierre et Marie Curie-Paris 6, EA 3500, Paris, F-75012 France,¹ AP-HP, hôpital Armand Trousseau, Service de Virologie, Paris, F-75012 France²

Received 13 August 2007/ Accepted 11 January 2008

Group A rotaviruses are the main cause of viral gastroenteritis in infants. The viral genome consists of 11 double-stranded RNA (dsRNA) segments. Dysfunction of the viral RNA polymerase can lead to gene rearrangements, which most often consist of partial sequence duplication of a dsRNA segment. Gene rearrangements have been detected in vivo during chronic infection in immunodeficient children or in vitro during passages at a high multiplicity of infection in cell culture, suggesting that these replication conditions lead to selective advantages favoring the recovery of viruses with rearranged genes. During acute rotavirus infection, the replication level is high, but the occurrence of rearrangement events has never been reported. By the use of a reverse transcription-PCR assay specifically designed to detect small numbers of copies of rearranged forms of segment 11 in a high background of its standard counterpart, we detected 12 rearrangement events among 161 cases (7.5%) of acute rotavirus infection in immunocompetent children. Strikingly, in all but one case, rearrangement took place at the same location within the short direct repeat AUGU sequence. For the unique case with a different rearrangement pattern, the rearrangement occurred within the direct repeat ACAAGUC that was specific for this isolate. In conclusion, we report the occurrence of segment 11 rearrangements during acute rotavirus infection in immunocompetent children. We show that under such conditions of infection, the viral RNA polymerase generates rearrangements which occur not at random but within direct repeats which might constitute hot spots for RNA recombination.

Published ahead of print on 23 January 2008.

These authors equally contributed to this work.

Present address: Service de Bactériologie-Virologie, hôpital Lariboisière 75475, Paris cedex 10, France.

Present address: Laboratoire de Virologie du CERVI, Groupe Hospitalier Pitié-Salpêtrière 75651, Paris cedex 13, France.