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SIV Latency in Macrophages in the CNS

Lucio Gama1, Celina Abreu1, Erin N Shirk1

  • 1Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, 21205, USA.

Current Topics in Microbiology and Immunology
|May 18, 2018
PubMed

Insights

Myeloid cells, not just CD4+ T cells, can harbor latent lentiviruses like HIV. This discovery suggests myeloid cells are a potential viral reservoir crucial for HIV eradication strategies.

Area of Science:

  • Virology
  • Immunology
  • Infectious Diseases

Background:

  • Lentiviruses, including HIV and SIV, establish persistent infections by evading host immune responses.
  • While HIV primarily targets CD4+ T cells, it also infects myeloid cells, contributing to tissue-specific diseases.
  • Antiretroviral therapy (ART) suppresses viral replication but fails to eliminate latent virus, leading to viral rebound upon treatment interruption.

Purpose of the Study:

  • To investigate the potential of myeloid cells as a latent reservoir for lentiviruses.
  • To develop a method for assessing latent lentiviral infection in myeloid cells.
  • To evaluate the role of myeloid cells in viral persistence and inform HIV eradication strategies.

Main Methods:

  • Adaptation of the quantitative viral outgrowth assay (QVOA) for assessing latently infected myeloid cells.
  • Application of the adapted QVOA in a SIV ART model using myeloid cells from blood and brain tissues.
  • In vitro reactivation assays to determine the infectious potential of reactivated virus from myeloid reservoirs.

Main Results:

  • Latent SIV was detected in myeloid cells from both blood and brain tissues in the SIV ART model.
  • Reactivation of latent SIV from myeloid cells resulted in the production of infectious virus in vitro.
  • These findings demonstrate that myeloid cells can harbor and release infectious lentiviruses.

Conclusions:

  • Myeloid cells represent a significant, yet underappreciated, latent reservoir for lentiviruses.
  • The presence of latent virus in myeloid cells has critical implications for HIV persistence and treatment failure.
  • Considering myeloid cells as a viral reservoir is essential for developing effective HIV eradication strategies.

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