title: HIV protease cleaves poly(A)-binding protein.
abstract: The PABP [poly(A)-binding protein] is able to interact with the 3' poly(A) tail of eukaryotic mRNA, promoting its translation. Cleavage of PABP by viral proteases encoded by several picornaviruses and caliciviruses plays a role in the abrogation of cellular protein synthesis. We report that infection of MT-2 cells with HIV-1 leads to efficient proteolysis of PABP. Analysis of PABP integrity was carried out in BHK-21 (baby-hamster kidney) and COS-7 cells upon individual expression of the protease from several members of the Retroviridae family, e.g. MoMLV (Moloney murine leukaemia virus), MMTV (mouse mammary tumour virus), HTLV-I (human T-cell leukaemia virus type I), SIV (simian immunodeficiency virus), HIV-1 and HIV-2. Moreover, protease activity against PABP was tested in a HeLa-cell-free system. Only MMTV, HIV-1 and HIV-2 proteases were able to cleave PABP in the absence of other viral proteins. Purified HIV-1 and HIV-2 proteases cleave PABP1 directly at positions 237 and 477, separating the two first RNA-recognition motifs from the C-terminal domain of PABP. An additional cleavage site located at position 410 was detected for HIV-2 protease. These findings indicate that some retroviruses may share with picornaviruses and caliciviruses the capacity to proteolyse PABP.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain. ealvarez@cnb.uam.es
authors.forename: Enrique
authors.initials: E
authors.lastname: Alvarez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Castelló
authors.forename: Luis
authors.initials: L
authors.lastname: Menéndez-Arias
authors.forename: Luis
authors.initials: L
authors.lastname: Carrasco
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008324:Mammary Tumor Virus, Mouse / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000201:enzymology / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012191:Retroviridae Proteins / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
chemical_list: C113920:EIF4G1 protein, human; C491300:EIF4G2 protein, human; D039603:Eukaryotic Initiation Factor-4G; D039102:Poly(A)-Binding Proteins; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C065184:p16 protease, Human immunodeficiency virus 2