Among ATF proteins, ATF4, a key transcription regulator of the integrated stress response (ISR), an evolutionarily conserved intra-cellular signaling network that coordinates cell responses to various environmental and pathological stress (51), has been previously associated with HIV infection, as it was identified as a factor that is upregulated during HIV-1 infection, thereby activating HIV replication and enhancing both Tat-independent and Tat-dependent viral gene expression (50, 52). This evidence concerns the gene TAT and HIV infectious disease.