A Quantitative Approach to SIV Functional Latency in Brain Macrophages

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Lentiviruses, including Human Immunodeficiency Virus (HIV) and Simian Immunodeficiency Virus (SIV), infect myeloid cells and CD4+ lymphocytes, causing acute and persistent infections.
• Antiretroviral therapy (ART) controls viral replication but does not eliminate virus-infected cells, leaving potential latent reservoirs.
• The role of myeloid cells as a persistent, latent reservoir for HIV has been underexplored, despite their presence in tissues like the brain, lungs, and spleen.

Purpose of the Study:

• To investigate the potential of myeloid cells as a latent reservoir for lentiviruses.
• To assess the capacity of latently infected myeloid cells to produce infectious virus, particularly in the context of ART suppression.
• To evaluate the implications of myeloid reservoirs for HIV eradication strategies.

Main Methods:

• Development of a quantitative viral outgrowth assay (QVOA) adapted for assessing latently infected myeloid cells in blood and brain.
• Utilized a well-characterized SIV-infected, ART-suppressed non-human primate (NHP) model.
• In vitro reactivation assays to determine the infectious potential of virus from myeloid reservoirs.

Main Results:

• Demonstrated that myeloid cells in both blood and brain harbor latent SIV during ART suppression.
• Showcased the ability of these latently infected myeloid cells to be reactivated and produce infectious virus in vitro.
• Provided the first evidence of myeloid cells acting as a latent reservoir capable of producing reactivatable virus.

Conclusions:

• Myeloid cells represent a significant, previously underestimated latent reservoir for lentiviruses.
• The presence of infectious virus in reactivated myeloid reservoirs poses a barrier to complete HIV eradication.
• Further research into targeting myeloid reservoirs is crucial for developing effective HIV cure strategies.