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Journal of Virology, June 2009, p. 6135-6148, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.00409-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Shared and Group-Specific Features of the Rotavirus RNA Polymerase Reveal Potential Determinants of Gene Reassortment Restriction{triangledown} ,{dagger}

Sarah M. McDonald,1 Daniel Aguayo,2 Fernando D. Gonzalez-Nilo,2 and John T. Patton1*

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20826-8026,1 Center for Bioinformatics and Molecular Simulations, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile2

Received 24 February 2009/ Accepted 31 March 2009

Rotaviruses (RVs) are nonenveloped, 11-segmented, double-stranded RNA viruses that are major pathogens associated with acute gastroenteritis. Group A, B, and C RVs have been isolated from humans; however, intergroup gene reassortment does not occur for reasons that remain unclear. This restriction might reflect the failure of the viral RNA-dependent RNA polymerase (RdRp; VP1) to recognize and replicate the RNA of a different group. To address this possibility, we contrasted the sequences, structures, and functions of RdRps belonging to RV groups A, B, and C (A-VP1, B-VP1, and C-VP1, respectively). We found that conserved amino acid residues are located within the hollow center of VP1 near the active site, whereas variable, group-specific residues are mostly surface exposed. By creating a three-dimensional homology model of C-VP1 with the A-VP1 crystallographic data, we provide evidence that these RV RdRps are nearly identical in their tertiary folds and that they have the same RNA template recognition mechanism that differs from that of B-VP1. Consistent with the structural data, recombinant A-VP1 and C-VP1 are capable of replicating one another's RNA templates in vitro. Nonetheless, the activity of both RdRps is strictly dependent upon the presence of cognate RV core shell protein A-VP2 or C-VP2, respectively. Together, the results of this study provide unprecedented insight into the structure and function of RV RdRps and support the notion that VP1 interactions may influence the emergence of reassortant viral strains.

* Corresponding author. Mailing address: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20826-8026. Phone: (301) 594-1615. Fax: (301) 496-8312. E-mail: jpatton{at}niaid.nih.gov

{triangledown} Published ahead of print on 8 April 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, June 2009, p. 6135-6148, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.00409-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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