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Establishment, Persistence, and Reactivation of Latent HIV-1 Infection in Renal Epithelial Cells.

Publication ,  Journal Article
Baker, EJ; Hughes, K; Travieso, T; Klotman, ME; Blasi, M
Published in: J Virol
July 27, 2022

HIV-1 persistence in different cell types presents the main obstacle to an HIV-1 cure. We have previously shown that the renal epithelium is a site of HIV-1 infection and that the kidney represents a separate viral compartment from blood. Whether renal cells can harbor latent virus that can be reactivated upon treatment with latency reversing agents (LRAs) is unknown. To address this question, we developed an in vitro HIV-1 latency model in renal tubule epithelial (RTE) cells using a dual color HIV-1 reporter virus, R7/E-/GFP/EF1a-mCherry (R7GEmC), and evaluated the effect of LRAs, both as single agents and in combination, on viral reactivation. Our data show that HIV-1 can establish latency in RTE cells early postinfection. While the pool of latently infected cells expanded overtime, the percentage of productively infected cells declined. Following LRA treatment only a small fraction of latently infected cells, both T cells and RTE cells, could be reactivated, and the drug combinations more effective in reactivating HIV transcription in RTE cells differed from those more active in T cells. Our study demonstrates that HIV can establish latency in RTE cells and that current LRAs are only marginally effective in inducing HIV-1 reactivation. This suggests that further study of LRA dynamics in non-T cells may be warranted to assess the suitability of LRAs as a sterilizing cure strategy. IMPORTANCE Anti-retroviral therapy (ART) has dramatically reduced HIV-related morbidity and mortality. Despite this success, a number of challenges remain, including the long-term persistence of multiple, clinically latent viral reservoirs capable of reactivation in the absence of ART. As efforts proceed toward HIV eradication or functional cure, further understanding of the dynamics of HIV-1 replication, establishment of latency and mechanisms of reactivation in reservoirs harboring the virus throughout the body is necessary. HIV-1 can infect renal epithelial cells and the expression of viral genes in those cells contributes to the development of HIV associated nephropathy (HIVAN) in untreated individuals. The significance of our work is in developing the first model of HIV-1 latency in renal epithelial cells. This model enhances our understanding of HIV-1 latency and persistence in the kidney and can be used to screen candidate latency reversing agents.

Duke Scholars

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

July 27, 2022

Volume

96

Issue

14

Start / End Page

e0062422

Location

United States

Related Subject Headings

  • Virus Latency
  • Virus Activation
  • Virology
  • Kidney
  • Humans
  • HIV-1
  • HIV Infections
  • Epithelial Cells
  • Cells, Cultured
  • CD4-Positive T-Lymphocytes
 

Citation

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Baker, E. J., Hughes, K., Travieso, T., Klotman, M. E., & Blasi, M. (2022). Establishment, Persistence, and Reactivation of Latent HIV-1 Infection in Renal Epithelial Cells. J Virol, 96(14), e0062422. https://doi.org/10.1128/jvi.00624-22
Baker, Erich J., Kelly Hughes, Tatianna Travieso, Mary E. Klotman, and Maria Blasi. “Establishment, Persistence, and Reactivation of Latent HIV-1 Infection in Renal Epithelial Cells.J Virol 96, no. 14 (July 27, 2022): e0062422. https://doi.org/10.1128/jvi.00624-22.
Baker EJ, Hughes K, Travieso T, Klotman ME, Blasi M. Establishment, Persistence, and Reactivation of Latent HIV-1 Infection in Renal Epithelial Cells. J Virol. 2022 Jul 27;96(14):e0062422.
Baker, Erich J., et al. “Establishment, Persistence, and Reactivation of Latent HIV-1 Infection in Renal Epithelial Cells.J Virol, vol. 96, no. 14, July 2022, p. e0062422. Pubmed, doi:10.1128/jvi.00624-22.
Baker EJ, Hughes K, Travieso T, Klotman ME, Blasi M. Establishment, Persistence, and Reactivation of Latent HIV-1 Infection in Renal Epithelial Cells. J Virol. 2022 Jul 27;96(14):e0062422.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

July 27, 2022

Volume

96

Issue

14

Start / End Page

e0062422

Location

United States

Related Subject Headings

  • Virus Latency
  • Virus Activation
  • Virology
  • Kidney
  • Humans
  • HIV-1
  • HIV Infections
  • Epithelial Cells
  • Cells, Cultured
  • CD4-Positive T-Lymphocytes