Viral replication. Once HIV enters a cell, undergoes reverse transcription, and is integrated into the nucleus (integration), several host transcriptional and viral activational factors stimulate viral replication (transcription). Regulatory proteins, such as Tat, Rev, and Nef, are generally produced early and, in the case of Tat, stimulate the virus to replicate. Rev-dependent messenger RNA (mRNA) usually results in unspliced or singly spliced RNA products via the "chaperone" effect of Rev, which escorts the unspliced message from the nucleus to the cytoplasm. Once in the cytoplasm, the long messages are translated into structural proteins, such as Gag, Pol, and Env, usually as a later event in the replication cycle (translation, late regulatory proteins). The production of these proteins is augmented by the help of late regulatory proteins such as Vif. Once the proteins and genomic RNA have been produced, they aggregate near the cell surface, where an immature virion buds on the cell membrane. After release of the immature virion from the cell, the activity of the protease gene results in development of a mature virion [9]. (RRE—Rev-responsive elements.) (Adapted from Hahn [8].