It is accepted the existence of restriction mechanisms operating during HIV-1 infection of resting T CD4 positive lymphocytes [49], possibly: (i) at the reverse transcription step related to SAMHD1 activity which results in hydrolysis of cellular dNTP pools [50, 51]; (ii) related to cellular miRNA activity against viral and cellular gene expression [52]; or (iii) due to particularly active APOBEC3Gs [53]. Here, CD4 is linked to HIV-1 infection.