Model of complementation between unintegrated and integrated HIV-1. (A) Viral transcription in the absence of integration generates all classes of viral transcripts, but only early proteins such as Tat, Rev, and Nef are synthesized at low levels. Tat and Nef can modulate cellular conditions. Viral replication does not occur without integration, but infection by a second virus can rescue the unintegrated viral genomes. (B) Coinfection of a cell by multiple particles can lead to accumulation of unintegrated viral DNA. However, an integrated provirus can rescue the genomes of the unintegrated viral DNA, preventing possible losses of viral genetic diversity. (C) Superinfection of a productively infected cell may not require new integration of the incoming virus, thus reducing steps required for viral replication and avoiding excessive integration to disrupt cellular function.