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Journal of Virology, November 2008, p. 11106-11116, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01402-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Group A Human Rotavirus Genomics: Evidence that Gene Constellations Are Influenced by Viral Protein Interactions{triangledown} ,{dagger}

Erica M. Heiman ,{ddagger},§ Sarah M. McDonald,{ddagger} Mario Barro, Zenobia F. Taraporewala, Tamara Bar-Magen,|| and John T. Patton*

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, MSC 8026, Room 6314, Bethesda, Maryland 20892-8026

Received 5 July 2008/ Accepted 3 September 2008

Group A human rotaviruses (HRVs) are the major cause of severe viral gastroenteritis in infants and young children. To gain insight into the level of genetic variation among HRVs, we determined the genome sequences for 10 strains belonging to different VP7 serotypes (G types). The HRVs chosen for this study, D, DS-1, P, ST3, IAL28, Se584, 69M, WI61, A64, and L26, were isolated from infected persons and adapted to cell culture to use as serotype references. Our sequencing results revealed that most of the individual proteins from each HRV belong to one of three genotypes (1, 2, or 3) based on their similarities to proteins of genogroup strains (Wa, DS-1, or AU-1, respectively). Strains D, P, ST3, IAL28, and WI61 encode genotype 1 (Wa-like) proteins, whereas strains DS-1 and 69M encode genotype 2 (DS-1-like) proteins. Of the 10 HRVs sequenced, 3 of them (Se584, A64, and L26) encode proteins belonging to more than one genotype, indicating that they are intergenogroup reassortants. We used amino acid sequence alignments to identify residues that distinguish proteins belonging to HRV genotype 1, 2, or 3. These genotype-specific changes cluster in definitive regions within each viral protein, many of which are sites of known protein-protein interactions. For the intermediate viral capsid protein (VP6), the changes map onto the atomic structure at the VP2-VP6, VP4-VP6, and VP7-VP6 interfaces. The results of this study provide evidence that group A HRV gene constellations exist and may be influenced by interactions among viral proteins during replication.

* Corresponding author. Mailing address: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, MSC 8026, Room 6314, Bethesda, MD 20892-8026. Phone: (301) 594-1615. Fax: (301) 496-8312. E-mail: jpatton{at}niaid.nih.gov

{triangledown} Published ahead of print on 10 September 2008.

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

{ddagger} These authors contributed equally to the manuscript.

§ Present address: UC Berkeley-UCSF Joint Medical Program, 570 University Hall, Berkeley, CA 94720.

Present address: Global Vaccines, Inc., P.O. Box 14827, Research Triangle Park, NC.

|| Present address: McGill AIDS Centre, Lady Davis Institute, Jewish General Hospital, 3755 Cote-Ste-Catherine Road, Montreal, QC H3T 1E2, Canada.

Journal of Virology, November 2008, p. 11106-11116, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01402-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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