HIV-1 protease cleaves eukaryotic initiation factor 4G and inhibits cap-dependent translation.
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.
Ventoso
I
I
Centro de Biologia Molecular Severo Ochoa, Universidad Autónoma de Madrid, Facultad de Ciencias, Cantoblanco, 28049 Madrid, Spain. iventoso@trasto.cbm.uam.es
Blanco
R
R
Perales
C
C
Carrasco
L
L
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D039603:Eukaryotic Initiation Factor-4G; D016333:HIV Protease / Q000378:metabolism*; D006868:Hydrolysis; D010448:Peptide Initiation Factors / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D012315:RNA Caps / Q000502:physiology*
D017931:DNA Primers; D039603:Eukaryotic Initiation Factor-4G; D010448:Peptide Initiation Factors; D012315:RNA Caps; D016333:HIV Protease