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Journal of Virology, February 2008, p. 1496-1504, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01779-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Rotavirus Infection Induces the Phosphorylation of eIF2{alpha} but Prevents the Formation of Stress Granules{triangledown}

Hilda Montero, Margarito Rojas, Carlos F. Arias, and Susana López*

Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, UNAM, Cuernavaca, Morelos 62210, México

Received 13 August 2007/ Accepted 12 November 2007

Early during the infection process, rotavirus causes the shutoff of cell protein synthesis, with the nonstructural viral protein NSP3 playing a vital role in the phenomenon. In this work, we have found that the translation initiation factor 2{alpha} (eIF2{alpha}) in infected cells becomes phosphorylated early after virus infection and remains in this state throughout the virus replication cycle, leading to a further inhibition of cell protein synthesis. Under these restrictive conditions, however, the viral proteins and some cellular proteins are efficiently translated. The phosphorylation of eIF2{alpha} was shown to depend on the synthesis of three viral proteins, VP2, NSP2, and NSP5, since in cells in which the expression of any of these three proteins was knocked down by RNA interference, the translation factor was not phosphorylated. The modification of this factor is, however, not needed for the replication of the virus, since mutant cells that produce a nonphosphorylatable eIF2{alpha} sustained virus replication as efficiently as wild-type cells. In uninfected cells, the phosphorylation of eIF2{alpha} induces the formation of stress granules, aggregates of stalled translation complexes that prevent the translation of mRNAs. In rotavirus-infected cells, even though eIF2{alpha} is phosphorylated these granules are not formed, suggesting that the virus prevents the assembly of these structures to allow the translation of its mRNAs. Under these conditions, some of the cellular proteins that form part of these structures were found to change their intracellular localization, with some of them having dramatic changes, like the poly(A) binding protein, which relocates from the cytoplasm to the nucleus in infected cells, a relocation that depends on the viral protein NSP3.

* Corresponding author. Mailing address: Instituto de Biotecnología, UNAM, Avenida Universidad 2001, Colonia Chamilpa, Cuernavaca, Morelos 62210, Mexico. Phone: (52) (777) 3291615. Fax: (52) (777) 3172388. E-mail: susana{at}ibt.unam.mx

{triangledown} Published ahead of print on 21 November 2007.

Journal of Virology, February 2008, p. 1496-1504, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01779-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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