HIV protease cleaves poly(A)-binding protein

Enrique Álvarez (1) , Alfredo Castelló , Luis Menéndez-Arias , Luis Carrasco

1 Department of Molecular and Cell Biology

The poly(A) binding protein (PABP) 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 an efficient proteolysis of PABP. Analysis of PABP integrity was carried out in BHK-21 and COS-7 cells upon individual expression of the protease from several members of the Retroviridae family, e.g. Moloney murine leukemia virus (MoMLV), mouse mammary tumor virus (MMTV), human T-cell leukemia virus type I (HTLV-I), simian immunodeficiency virus (SIV), human immunodeficiency virus type 1 (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 absence of other viral proteins. Purified HIV-1 and HIV-2 proteases directly cleave PABP1 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 proteolyze PABP.

Mots clés: Life Sciences

Enrique Álvarez, Alfredo Castelló, Luis Menéndez-Arias, Luis Carrasco. HIV protease cleaves poly(A)-binding protein. Biochemical Journal, 2006, 396 (2), pp.219-226. ⟨10.1042/BJ20060108⟩. ⟨hal-00478519⟩