Changes in the cellular microRNA profile by the intracellular expression of HIV-1 Tat regulator: A potential mechanism for resistance to apoptosis and impaired proliferation in HIV-1 infected CD4+ T cells.

HIV-1 induces changes in the miRNA expression profile of infected CD4+ T cells that could improve viral replication. HIV-1 regulator Tat modifies the cellular gene expression and has been appointed as an RNA silencing suppressor. Tat is a 101-residue protein codified by two exons that regulates the elongation of viral transcripts.

The presence of HIV-1 Tat protein second exon delays fas protein-mediated apoptosis in CD4+ T lymphocytes: a potential mechanism for persistent viral production.

HIV-1 replication is efficiently controlled by the regulator protein Tat (101 amino acids) and codified by two exons, although the first exon (1-72 amino acids) is sufficient for this process. Tat can be released to the extracellular medium, acting as a soluble pro-apoptotic factor in neighboring cells. However, HIV-1-infected CD4(+) T lymphocytes show a higher resistance to apoptosis.

Mechanisms of RNA interference in the HIV-1-host cell interplay.

The RNA interference pathway is a mechanism to regulate gene expression that acts in mammalian antiviral immunity as a complement of interferon- and cytokine-based innate immunity. RNA interference has been proposed as an ancient mechanism against viruses since several components of this system show an effect against viral replication. In fact, protein effectors of this pathway, as well as synthesized microRNA, act against HIV-1, exerting a partial control over HIV-1 latency and replication.

Protein kinase Ctheta is a specific target for inhibition of the HIV type 1 replication in CD4+ T lymphocytes.

Integration of HIV-1 genome in CD4(+) T cells produces latent reservoirs with long half-life that impedes the eradication of the infection. Control of viral replication is essential to reduce the size of latent reservoirs, mainly during primary infection when HIV-1 infects CD4(+) T cells massively. The addition of immunosuppressive agents to highly active antiretroviral therapy during primary infection would suppress HIV-1 replication by limiting T cell activation, but these agents show potential risk for causing lymphoproliferative disorders.

Dual role of host cell factors in HIV-1 replication: restriction and enhancement of the viral cycle.

Once HIV-1 enters the target cell, the first goal in the viral cycle is to integrate into the cellular chromosomes. The irreversible integration as a provirus allows HIV-1 to persist in the infected cell in a quiescent or latent stage that leads to viral escape from immune response and current antiviral treatment. HIV-1 replication is absolutely dependent on different cellular and viral factors that initiate viral expression, acting at the long terminal repeat of the integrated provirus.