A Human Rotavirus with Rearranged Genes 7 and 11 Encodes a Modified NSP3 Protein and Suggests an Additional Mechanism for Gene Rearrangement

Abstract

A human rotavirus (isolate M) with an atypical electropherotype with 14 apparent bands of double-stranded RNA was isolated from a chronically infected immunodeficient child. MA-104 cell culture adaptation showed that the M isolate was a mixture of viruses containing standard genes (M0) or rearranged genes: M1 (containing a rearranged gene 7) and M2 (containing rearranged genes 7 and 11). The rearranged gene 7 of virus M1 (gene 7R) was very unusual because it contained two complete open reading frames (ORF). Moreover, serial propagation of virus M1 in cell culture indicated that gene 7R rapidly evolved, leading to a virus with a deleted gene 7R (gene 7R⌬). Gene 7R⌬ coded for a modified NSP3 protein (NSP3m) of 599 amino acids (aa) containing a repetition of aa 8 to 296. The virus M3 (containing gene 7R⌬) was not defective in cell culture and actually produced NSP3m. The rearranged gene 11 (gene 11R) had a more usual pattern, with a partial duplication leading to a normal ORF followed by a long 3 untranslated region. The rearrangement in gene 11R was almost identical to some of those previously described, suggesting that there is a hot spot for gene rearrangements at a specific location on the sequence. It has been suggested that in some cases the existence of short direct repeats could favor the occurrence of rearrangement at a specific site. The computer modeling of gene 7 and 11 mRNAs led us to propose a new mechanism for gene rearrangements in which secondary structures, besides short direct repeats, might facilitate and direct the transfer of the RNA polymerase from the 5 to the 3 end of the plus-strand RNA template during the replication step.

Frequent rearrangement may explain the structural heterogeneity in the 11th genome segment of lapine rotaviruses — Short communication

“…One explanation is that rotavirus might determine a prolonged persistence in rabbits kept in commercial herds, thus increasing the odds for genomic rearrangements. This ecological background seems to parallel with that seen in human rotaviruses with a rearranged genome, which have been isolated most frequently from chronically infected immunocompromised patients (Pedley et al, 1984;Hundley et al, 1987;Palombo et al, 1998;Gault et al, 2001;Mori et al, 2002).…”

Inter-segment complementarity in orbiviruses: a driver for co-ordinated genome packaging in the Reoviridae?

“…First, based on analysis of defective interfering segments and other naturally occurring rearrangements of genome segments, members of the Reoviridae have been shown to consistently retain the 59-and 39-end regions in their normal position (Ballard et al, 1992;Feenstra et al, 2014;Gault et al, 2001;González et al, 1989;Gorziglia et al, 1989;Hua & Patton, 1994;Hundley et al, 1985;Matsui et al, 1990;Méndez et al, 1992;Pedley et al, 1984;Scott et al, 1989;Tian et al, 1993). This indicates that these regions contain all the cis-acting sequences needed to regulate packaging, genome replication and transcription of the segment.…”

Rapid mapping of functional cis-acting RNA elements by recovery of virus from a degenerate RNA population: application to genome segment 10 of bluetongue virus

“…Defective interfering segments and other naturally occurring rearrangements of genome segments in members of the Reoviridae have been shown to consistently retain the 59 and the 39 end regions of the affected genome segment (Ballard et al, 1992;Desselberger, 1996;Feenstra et al, 2014;Gault et al, 2001;González et al, 1989;Gorziglia et al, 1989;Hua & Patton, 1994;Hundley et al, 1985;Matsui et al, 1990;Méndez et al, 1992;Palombo et al, 1998;Pedley et al, 1984;Scott et al, 1989;Shen et al, 1994;Tian et al, 1993). In each case the two regions are retained in their normal positions at the termini of the segment, indicating that they contain the cis-acting sequences which regulate transcription, genome replication and packaging of the segment.…”