Deamination-independent inhibition of viral replication. In virus-producing cells, A3 and AID proteins are present in cytoplasmic complexes (left). AID is a shuttling protein and its nuclear activity may block cell proliferation and the number of infected cells. Alternatively, multiple APOBEC proteins may inhibit viral RNA translation. In the case of murine leukemia viruses, several different virally specified inhibitors, such as p50 and glycoGag (gGag) are produced in infected cells. The p50 protein prevents A3 incorporation into virions, whereas gGag is incorporated into virus particles to promote their stability, allowing normal proviral DNA synthesis in recipient cells (right). If gGag is present in viral particles, A3 may be incorporated into virions, leading to reduced proviral DNA. If virion RNA is packaged in the absence of gGag, viral cores are unstable and allow A3 enzymes in recipient cells to block reverse transcription. RT = reverse transcriptase.