The HIV-1 Life Cycle
Lab member Dyana Terri Saenz drew this diagram to highlight major events in the life cycle of HIV and other lentiviruses. After binding to CD4 and a co-receptor (CCR5 or CXCR4), fusion with the cell membrane results in entry of the viral core into the cytoplasm. Reverse transcription and uncoating occur, and at this stage the viral complex is vulnerable to species-specific defense mechanisms, e.g., restriction factors such as APOBEC3 proteins or TRIM5alpha. The complex must then be imported into the nucleus and become integrated into a host chromosome. The protein LEDGF/p75 acts as a cofactor during integration. During viral production, the Rev protein enables bypassing of the cellular splicing checkpoint for unspliced (genomic) and partially spliced mRNAs. The genomic RNA must then be preferentially packaged (encapsidated) versus cellular and splice viral RNAs by the assembling virion. Budding occurs and the particle matures by protease cleavage of a large precursor protein. One lab project has developed new methods to figure out where and when in the cell the genomic RNA becomes encapsidated.