HIV Expression in Infected T Cell Clones

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Antiretroviral therapy (ART) suppresses HIV-1 replication but does not eliminate the virus.
• The primary barrier to an HIV-1 cure is the persistence of infected cells harboring replication-competent proviruses.
• Viral latency and cellular proliferation are key determinants of HIV-1 persistence.

Purpose of the Study:

• To review the genetic, epigenetic, cellular, and immunological factors influencing HIV-1 transcriptional suppression.
• To discuss the clonal expansion of HIV-1 reservoir T cells.
• To explore the interdependencies among these determinants and their implications for HIV-1 persistence.

Main Methods:

• This review synthesizes existing research on HIV-1 persistence.
• It examines the mechanisms of viral latency and cellular proliferation in CD4+ T cells.
• The review discusses the interplay between genetic, epigenetic, cellular, and immunological factors.

Main Results:

• HIV-1 transcriptional suppression (latency) allows infected cells to evade immune detection.
• CD4+ T cell proliferation can facilitate HIV-1 propagation without detrimental viral gene expression.
• Selective pressures on ART favor the expansion of latently infected cell clones.

Conclusions:

• Incomplete or reversed latency in expanding clones can lead to persistent low-level viremia and rebound after treatment cessation.
• Understanding the determinants of viral latency and clonal expansion is crucial for developing strategies to eliminate the HIV-1 reservoir.
• Targeting these persistence mechanisms may offer new avenues for achieving a functional HIV-1 cure.