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JVI Accepts, published online ahead of print on 23 January 2008
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J. Virol. doi:10.1128/JVI.01770-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Rearrangements of rotavirus genomic segment 11 are generated during acute infection of immunocompetent children and do not occur at random

Nathalie SCHNEPF, Claire DEBACK, Axelle DEHEE, Elyanne GAULT, Nathalie PAREZ, and Antoine GARBARG-CHENON*

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

* To whom correspondence should be addressed. Email: a.chenon{at}trs.ap-hop-paris.fr.


   Abstract

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 in 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 high MOI in cell culture, suggesting that these replication conditions lead to selective advantages favoring the recovery of viruses with rearranged genes. During acute rotavirus infection, replication level is high, but the occurrence of rearrangement events has never been reported. By the use of a RT-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 of 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 do not occur at random, but within direct repeats which might constitute hot spots for RNA recombination.







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