In addition to picornavirus L pro and 2A pro , proteases from other viruses can also cleave eIF4G. The protease of human immunodeficiency virus type-1 (HIV-1) hydrolyzes eIF4GI during infection of human CD4+ cells [149] . The cleavage of eIF4GI takes place at positions 718, 721, and Journal of Biomedicine and Biotechnology 9 1125, separating it in three domains ( Figure 3 ) [149, 150] . Interestingly, HIV-1 protease efficiently cleaves eIF4GI, but not eIF4GII, both in cell-free systems and in mammalian cells [151] . The differential sensitivity of eIF4GI and eIF4GII to HIV-1 protease is more selective than that observed with picornaviral 2A proteases [122, 123] . HIV-1 protease also cleaves PABP at positions 237 and 477 separating the two first RNA-recognition motifs from the C-terminal domain of PABP [152] . Cleavage of eIF4GI and PABP by HIV-1 protease is sufficient to inhibit the translation of capped and polyadenylated mRNAs in cell-free systems, as well as in transfected cells [127, 151] . In contrast, IRES-driven translation is unaffected or even enhanced by HIV-1 PR after cleavage of both eIF4GI and PABP [127, 151] . Moreover, the translation of capped and polyadenylated HIV-1 genomic mRNA remains unaffected in HeLa extracts under these conditions suggesting that viral protein synthesis might persist at late phases of HIV-1 infection where those factors are cleaved [127] . In contrast, a previous report claimed that the hydrolysis of eIF4GI impaired the translation of both capped and IRES-driven mRNAs in reticulocyte lysate assays [150] . However, the different effect observed by these authors on IRES-driven translation can be due to differences already reported between HeLa extract and RRL [143, 153] . In addition, eIF4G cleavage is executed by proteases from other retrovirus species, such as HIV-2, simian immunodeficiency virus (SIV), human T-cell leukemia virus (HTLV-1), Moloney murine leukemia virus (MoMLV), and mouse mammary tumor virus (MMTV). These proteases hydrolyze eIF4GI and eIF4GII with different cleavage patterns and kinetics [134] . And indeed, several retroviruses, including HIV, SIV, and MoMLV, promote the translation of their gag gene products by internal ribosome entry, indicating that eIF4G cleavage could be compatible with viral protein synthesis in infected cells [154] [155] [156] . Furthermore, cleavage of eIF4GI and eIF4GII also occurs in feline calicivirusinfected cells although the cleavages occur at different sites to those observed for picornavirus proteases [157] . In addition, the 3C-like protease of two caliciviruses, like PV 3C pro , cleaves PABP perhaps as a complementary strategy to inhibit cellular translation [158] . The fact that proteases from many picornaviruses, retroviruses and caliciviruses, target eIF4G, and, in some cases, PABP, strongly suggest that those viruses may share a common mechanism to regulate cellular and viral translation. However, further investigation is required to determine the specific contribution of eIF4GI, eIF4GII and PABP to the shutoff of host-cell translation and virus protein synthesis.