From the Guidelines
The life cycle of HIV begins with attachment to a CD4+ T cell, followed by fusion, reverse transcription, integration, and replication, ultimately leading to the depletion of CD4+ T cells and weakening of the immune system. This process is complex and involves multiple stages, including attachment, fusion, reverse transcription, integration, replication, and maturation. The virus attaches to the CD4+ T cell using its gp120 protein to bind to the CD4 receptor and a co-receptor (usually CCR5 or CXCR4) 1. After attachment, the virus fuses with the cell membrane and releases its contents into the cell. The viral RNA is then converted to DNA by the enzyme reverse transcriptase, a process prone to errors that creates viral mutations. This viral DNA travels to the cell nucleus and integrates into the host cell's DNA using the viral enzyme integrase, creating a provirus. The provirus may remain dormant or begin producing new viral components using the cell's machinery. Viral proteins and RNA assemble at the cell membrane, and immature viral particles bud from the cell surface. Finally, the viral enzyme protease cleaves long protein chains into functional viral proteins, creating mature infectious viruses that can infect other cells.
Key aspects of the HIV life cycle include:
- Attachment to CD4+ T cells using gp120 protein and co-receptors
- Fusion with the cell membrane and release of viral contents
- Reverse transcription of viral RNA to DNA using reverse transcriptase
- Integration of viral DNA into the host cell's DNA using integrase
- Replication of the virus using the host cell's machinery
- Maturation of the virus through protease cleavage of protein chains
Antiretroviral medications target different stages of this life cycle, including entry inhibitors, reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors 1. Understanding the HIV life cycle is crucial for the development of effective treatment strategies and prevention methods, as highlighted in recent guidelines and recommendations 1.
From the Research
Life Cycle of HIV
The life cycle of HIV involves several steps necessary for the successful infection of human target cells.
- The RNA genome enters the cytoplasm after the fusion of the viral membrane and that of the target cell 2.
- The RNA genome is then converted to DNA form through the process of reverse transcription 2.
- The DNA genome is then integrated into the host cell DNA, which depends on the enzymatic activity of HIV-1 integrase and involves different cellular factors that influence the selection of integration sites 3.
- Next, viral proteins and more copies of the viral genome are produced 2.
- These components assemble to form new virions that are then able to propagate 2.
Key Events in the Life Cycle
- Integration of the viral genome into host DNA is the only nuclear event in the viral life cycle that can be pharmacologically targeted with current therapies 3.
- The selection of integration site has functional consequences for viral transcription, which usually follows the integration event 3.
- In resting CD4+ T cells, the viral genome can be silenced for long periods of time, which leads to the generation of a latent reservoir of quiescent integrated HIV-1 DNA 3.