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Journal of Virology, March 2003, p. 3291-3296, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.3291-3296.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Structures of Rotavirus Reassortants Demonstrate Correlation of Altered Conformation of the VP4 Spike and Expression of Unexpected VP4-Associated Phenotypes

Joseph B. Pesavento,1,2,{dagger} Angela M. Billingsley,1 Ed J. Roberts,1 Robert F. Ramig,3 and B. V. Venkataram Prasad1,2,3*

Verna and Marrs McLean Department of Biochemistry and Molecular Biology,1 W. M. Keck Center for Computational Biology,2 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 770303

Received 25 July 2002/ Accepted 4 December 2002

Numerous prior studies have indicated that viable rotavirus reassortants containing structural proteins of heterologous parental origin may express unexpected phenotypes, such as changes in infectivity and immunogenicity. To provide a structural basis for alterations in phenotypic expression, a three-dimensional structural analysis of these reassortants was conducted. The structures of the reassortants show that while VP4 generally maintains the parental structure when moved to a heterologous protein background, in certain reassortants, there are subtle alterations in the conformation of VP4. The alterations in VP4 conformation correlated with expression of unexpected VP4-associated phenotypes. Interactions between heterologous VP4 and VP7 in reassortants expressing unexpected phenotypes appeared to induce the conformational alterations seen in VP4.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-5686. Fax: (713) 798-1625. E-mail: vprasad{at}bcm.tmc.edu.

{dagger} Present address: Computational and System Biology Division, Lawrence Livermore National Laboratory, Univeristy of California, Livermore, CA 94551.

Journal of Virology, March 2003, p. 3291-3296, Vol. 77, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.5.3291-3296.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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