However, inhibition of cap-dependent translation initiation can occur independent of PKR activation. Indeed, the HIV-1 Vpr protein is capable of inducing G2 arrest in cultured CD4+ T cells (48, 49 and references therein), and, during such arrest, cap-dependent translation initiation is severely impaired (50) . Another possible strategy to circumvent the problem caused by this situation is the use of a cap-independent mechanism by HIV-1 to initiate the translation of its full-length mRNA (25, 45) . The virus would thus continue to express Gag and Gag-Pol and would maintain a frameshift efficiency that is optimal for its replication. An internal ribosomal entry site (IRES) was identified in the 5 0 UTR region of HIV-1 full-length mRNA (51) and another IRES was found in the beginning of the gag coding sequence (52) . IRES have also been found in HIV type 2 (53) and in simian immunodeficiency virus (54) , two viruses related to HIV-1. However, the use of an IRES by HIV-1 in the context of replication-competent viruses remains to be proven (45) . The two strategies that are described above are not mutually exclusive. HIV-1 could first counteract changes in cap-dependent translation initiation by inhibiting PKR, until a larger stress in the cellular environment severely perturbs cap-dependent initiation. The virus would then switch to an IRES-driven mode to translate its full-length mRNA.