The essential steps in the life cycle of HIV-1. The first step is the attachment of the virus particle to receptors on the cell surface. The HIV-1 RNA genome then enters the cytoplasm as part of a nucleoprotein complex. The viral RNA genome is reverse-transcribed into a DNA duplex, which has terminal duplications known as long terminal repeats (LTRs). The linear viral DNA molecule is part of the preintegration complex that enters the nucleus. In the nucleus, unintegrated viral DNA is found in both linear and circular forms. The unintegrated circular forms of viral DNA have either one or two LTRs, are byproducts of the integration process, and are found exclusively in the nucleus. The linear unintegrated viral DNA is the precursor of integrated proviral DNA, which is a stable structure that remains indefinitely in the host-cell genome and serves as a template for viral transcription. Transcription of the proviral DNA template and alternative RNA splicing creates spliced viral RNA species encoding the viral accessory proteins, including Tat, Rev, and Nef, and the unspliced viral RNA encoding the viral structural proteins, including the Gag–Pol precursor protein. All the viral transcripts are exported into the cytoplasm, where translation and assembly and processing of the retroviral particle take place. The cycle is completed by the release of infectious retroviral particles from the cell. (Figure adapted from ; reproduced, with permission, from Massachusetts Medical Society © 1999).