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HIV-1 Protease Cleaves Eukaryotic Initiation Factor 4G and Inhibits Cap-dependent Translation

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Specialty Science
Date 2001 Oct 19
PMID 11606767
Citations 61
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Abstract

Several animal viruses inhibit host protein synthesis, but only some members of the picornavirus group are known to do so by cleaving translation initiation factor eIF4G. Here we report that infection of human CD4(+) cells with HIV-1 also leads to proteolysis of eIF4G and profound inhibition of cellular translation. Purified HIV-1 protease directly cleaves eIF4GI at positions 678, 681, and 1086, separating the three domains of this initiation factor. Proteolysis of eIF4GI by HIV-1 protease, as with poliovirus 2A protease, inhibits protein synthesis directed by capped mRNAs but allows internal ribosome entry site-driven translation. These findings indicate that HIV-1, a member of retrovirus group, shares with picornaviruses the capacity to proteolyze eIF4G.

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References
1.
Morino S, Imataka H, Svitkin Y, Pestova T, Sonenberg N . Eukaryotic translation initiation factor 4E (eIF4E) binding site and the middle one-third of eIF4GI constitute the core domain for cap-dependent translation, and the C-terminal one-third functions as a modulatory region. Mol Cell Biol. 1999; 20(2):468-77. PMC: 85104. DOI: 10.1128/MCB.20.2.468-477.2000. View

2.
Ventoso I, Barco A, Carrasco L . Genetic selection of poliovirus 2Apro-binding peptides. J Virol. 1998; 73(1):814-8. PMC: 103896. DOI: 10.1128/JVI.73.1.814-818.1999. View

3.
Gingras A, Raught B, Sonenberg N . eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem. 2000; 68:913-63. DOI: 10.1146/annurev.biochem.68.1.913. View

4.
Aragon T, de la Luna S, Novoa I, Carrasco L, Ortin J, Nieto A . Eukaryotic translation initiation factor 4GI is a cellular target for NS1 protein, a translational activator of influenza virus. Mol Cell Biol. 2000; 20(17):6259-68. PMC: 86100. DOI: 10.1128/MCB.20.17.6259-6268.2000. View

5.
Thompson S, Sarnow P . Regulation of host cell translation by viruses and effects on cell function. Curr Opin Microbiol. 2000; 3(4):366-70. DOI: 10.1016/s1369-5274(00)00106-5. View