Transcription from preintegrated or unintegrated DNA. Prior to integration, or if integration is blocked, transcription from unintegrated cDNA may still occur, the template for which is unknown. Virally imported Vpr is important in the initial stages of viral gene transcription. Translation of multiply-spliced RNA (msRNA) transcripts leads to expression of Tat, Nef and Rev. Levels of Rev are insufficient to lead to the export of singly spliced and unspliced transcripts. Rev is thought to later interfere with the integration process and to thereby inhibit superinfection. Tat and Nef collectively lead to increased cellular activation in resting T-cells. Newly synthesized Tat will also promote viral gene transcription. Nef downregulates cell surface CD4, CXCR4, CCR5 and MHC-I (HLA Class I), thereby limiting superinfection, signal transduction and likely resulting evasion from cytotoxic T-lymphocytes. Preintegration transcription of viral genes has also been linked to altered cytokine secretion in both resting T-cells and macrophages.