A widely distributed HIV-1 provirus elimination assay to evaluate latency-reversing agents in vitro

Matsuda, Kouki; Islam, Saiful; Takada, Toru; Tsuchiya, Kiyoto; Tan, Benjy J.Y.; Hattori, Shin-ichiro; Katsuya, Hiroo; Kitagawa, Kosaku; Kim, Kwang Su; Matsuo, Misaki; Sugata, Kenji; Delino, Nicole S.; Gatanaga, Hiroyuki; Yoshimura, Kazuhisa; Matsushita, Shuzo; Mitsuya, Hiroaki; Iwami, Shingo; Satou, Yorifumi; Maeda, Kenji

doi:10.1016/j.crmeth.2021.100122

Cited by 11 publications

(19 citation statements)

References 68 publications

(122 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To the best of our knowledge, the current study is the first to successfully identify a latent cell subset with integrated proviruses that showed transient expression, which was subsequently terminated (R + ). Using bulk integration site analysis, we first verified the generation of heterogeneous clones in our HIV-Tocky in vitro model as previously reported in our WIPE assay model 22 . R+ proviruses demonstrated distinct integration features compared with other Timer populations.…”

Section: Discussionmentioning

confidence: 75%

“…HIV-1 establishes its reservoir at an early stage of infection in vivo 21 , 60 – 63 . However, elucidating the mechanisms of latency establishment necessitates marking very rare latent infected cells 64 which in turn requires the use of several in vitro models that could recapitulate the situation in vivo 22 , 26 , 38 , 65 . Despite recent revolutionary advances in scrutinizing latent reservoirs ex vivo at the single-cell level 16 , 66 – 68 , the most recent report by Sun et al concluded the inability to identify a single universal marker for latently infected cells 69 .…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, utilizing HIV-1 in vitro reporter models has widely aided the advents in eradication strategies. We previously established the widely distributed provirus elimination assay (WIPE assay) as an in vitro HIV infection model with hundreds of infected clones that can be maintained for several months 22 . This model recapitulated the complexity of infected cells reported for in vivo HIV-1 infection, as well as the persistence of defective HIV-1 proviruses.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

HIV-Tocky system to visualize proviral expression dynamics

Reda,

Monde,

Sugata

et al. 2024

Commun Biol

Self Cite

View full text Add to dashboard Cite

Determinants of HIV-1 latency establishment are yet to be elucidated. HIV reservoir comprises a rare fraction of infected cells that can survive host and virus-mediated killing. In vitro reporter models so far offered a feasible means to inspect this population, but with limited capabilities to dissect provirus silencing dynamics. Here, we describe a new HIV reporter model, HIV-Timer of cell kinetics and activity (HIV-Tocky) with dual fluorescence spontaneous shifting to reveal provirus silencing and reactivation dynamics. This unique feature allows, for the first time, identifying two latent populations: a directly latent, and a recently silenced subset, with the latter having integration features suggestive of stable latency. Our proposed model can help address the heterogeneous nature of HIV reservoirs and offers new possibilities for evaluating eradication strategies.

show abstract

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

HIV-Tocky system to visualize proviral expression dynamics

Reda,

Monde,

Sugata

et al. 2024

Commun Biol

Self Cite

View full text Add to dashboard Cite

show abstract

“…HIV-1 establishes its reservoir at an early stage of infection in vivo 21,[55][56][57][58] . However, elucidating the mechanisms of latency establishment necessitates marking very rare latent infected cells 59 which in turn requires the use of several in vitro models that could recapitulate the situation in vivo 22,26,37,60 . Despite recent revolutionary advances in scrutinizing latent reservoirs ex vivo at the single-cell level 16,[61][62][63] , the most recent report by Sun et al concluded the inability to identify a single universal marker for latently infected cells 64 .…”

Section: Discussionmentioning

confidence: 99%

HIV-Tocky system to visualize proviral expression dynamics

Satou,

Reda,

Monde

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Determinants of HIV-1 latency establishment are yet to be elucidated. HIV reservoir comprises a rare fraction of infected cells that can survive host and virus-mediated killing. In vitro reporter models so far offered a feasible means to inspect this population, but with limited capabilities to dissect provirus silencing dynamics. Here, we describe a new HIV reporter model; HIV-Timer of cell kinetics and activity (HIV-Tocky) with dual fluorescence spontaneous shifting to reveal provirus silencing and reactivation dynamics. This unique feature allowed; for the first time, identifying two latent populations: a directly latent, and a recently silenced subset, with the latter having integration features suggestive of stable latency. Our proposed model can help address the heterogeneous nature of HIV reservoirs and offers new possibilities for evaluating eradication strategies.

show abstract

“…However, this approach has several issues, including the potential uncontrolled virus reactivation and associated immune compromise [ 15 ]. Moreover, most latently infected cells are not “uniform”; they cannot or do not respond to a single reactivator agent such as histone deacetylases or protein kinase C activators, suggesting different mechanisms of silencing and reactivation [ 16 , 17 , 18 , 19 ]. In addition, the reactivation mechanism depends on the cell type infected, including different cell populations, differentiation stage, proliferation, tissue compartmentalization, and cell lineage.…”

Section: Introductionmentioning

confidence: 99%

The Role of Pannexin-1 Channels in HIV and NeuroHIV Pathogenesis

Hernandez

Eugenin

2022

Cells

View full text Add to dashboard Cite

The human immunodeficiency virus-1 (HIV) enters the brain shortly after infection, leading to long-term neurological complications in half of the HIV-infected population, even in the current anti-retroviral therapy (ART) era. Despite decades of research, no biomarkers can objectively measure and, more importantly, predict the onset of HIV-associated neurocognitive disorders. Several biomarkers have been proposed; however, most of them only reflect late events of neuronal damage. Our laboratory recently identified that ATP and PGE2, inflammatory molecules released through Pannexin-1 channels, are elevated in the serum of HIV-infected individuals compared to uninfected individuals and other inflammatory diseases. More importantly, high circulating ATP levels, but not PGE2, can predict a decline in cognition, suggesting that HIV-infected individuals have impaired ATP metabolism and associated signaling. We identified that Pannexin-1 channel opening contributes to the high serological ATP levels, and ATP in the circulation could be used as a biomarker of HIV-associated cognitive impairment. In addition, we believe that ATP is a major contributor to chronic inflammation in the HIV-infected population, even in the anti-retroviral era. Here, we discuss the mechanisms associated with Pannexin-1 channel opening within the circulation, as well as within the resident viral reservoirs, ATP dysregulation, and cognitive disease observed in the HIV-infected population.

show abstract

A widely distributed HIV-1 provirus elimination assay to evaluate latency-reversing agents in vitro

Cited by 11 publications

References 68 publications

HIV-Tocky system to visualize proviral expression dynamics

HIV-Tocky system to visualize proviral expression dynamics

HIV-Tocky system to visualize proviral expression dynamics

The Role of Pannexin-1 Channels in HIV and NeuroHIV Pathogenesis

Contact Info

Product

Resources

About