The retroviral life cycle begins in the nucleus of an infected cell. At this stage of the life cycle the retroviral genome is a DNA element integrated into and covalently attached to the DNA of the host cell.The genome of the virus is of approximately 8-12 kilobases of DNA (depending upon the retroviral species). Full-length genomic mRNA is made initiating at the beginning ofthe R (repeat) at the 5' LTR (Long Terminal Repeat).The free particle can infect new cells by binding to a cell surface receptor. The specificity of the virus-cell interaction is determined largely by the envelope protein(s) of the retrovirus. Infection leads to injection of the virus nucleoprotein core (consisting mostly of gag-derived proteins, full-length genomic RNA, and the reverse transcriptase protein).

Once inside the cell, the nucleoprotein complex accesses intracellular DNA nucleotide triphosphate pools, whereupon the reverse transcriptase protein initiates creation of a double-stranded DNA copy of the genome of the virus in preparation for integration into the host cell chromosome. Upon completion of reverse transcription, the viral enzyme Integrase searches the DNA for an appropriate "home", whereupon the integrase clips the host DNA and sews the double-stranded DNA into the host DNA (see below). The virus is now prepared to initiate a new round of replication.