The latency-reversing agent HODHBt synergizes with IL-15 to enhance cytotoxic function of HIV-specific T cells Article Swipe
Dennis C. Copertino
,
Carissa S. Holmberg
,
Jared Weiler
,
Adam R. Ward
,
J. Natalie Howard
,
Callie Levinger
,
Alina P.S. Pang
,
Michael J. Corley
,
Friederike Dündar
,
Paul Zumbo
,
Doron Betel
,
Rajesh T. Gandhi
,
Deborah K. McMahon
,
Ronald J. Bosch
,
Noemi Linden
,
Bernard Macatangay
,
Joshua C. Cyktor
,
Joseph J. Eron
,
John W. Mellors
,
Colin Kovacs
,
Erika Benko
,
Alberto Bosque
,
R. Brad Jones
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.169028
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.169028
IL-15 is under clinical investigation toward the goal of curing HIV infection because of its abilities to reverse HIV latency and enhance immune effector function. However, increased potency through combination with other agents may be needed. 3-Hydroxy-1,2,3-benzotriazin-4(3H)-one (HODHBt) enhances IL-15-mediated latency reversal and NK cell function by increasing STAT5 activation. We hypothesized that HODHBt would also synergize with IL-15, via STAT5, to directly enhance HIV-specific cytotoxic T cell responses. We showed that ex vivo IL-15 + HODHBt treatment markedly enhanced HIV-specific granzyme B-releasing T cell responses in PBMCs from antiretroviral therapy-suppressed (ART-suppressed) donors. We also observed upregulation of antigen processing and presentation in CD4+ T cells and increased surface MHC-I. In ex vivo PBMCs, IL-15 + HODHBt was sufficient to reduce intact proviruses in 1 of 3 ART-suppressed donors. Our findings reveal the potential for second-generation IL-15 studies incorporating HODHBt-like therapeutics. Iterative studies layering on additional latency reversal or other agents are needed to achieve consistent ex vivo reservoir reductions.
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Concepts
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1172/jci.insight.169028
- OA Status
- gold
- Cited By
- 11
- References
- 73
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4385840317
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4385840317Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1172/jci.insight.169028Digital Object Identifier
- Title
-
The latency-reversing agent HODHBt synergizes with IL-15 to enhance cytotoxic function of HIV-specific T cellsWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-08-15Full publication date if available
- Authors
-
Dennis C. Copertino, Carissa S. Holmberg, Jared Weiler, Adam R. Ward, J. Natalie Howard, Callie Levinger, Alina P.S. Pang, Michael J. Corley, Friederike Dündar, Paul Zumbo, Doron Betel, Rajesh T. Gandhi, Deborah K. McMahon, Ronald J. Bosch, Noemi Linden, Bernard Macatangay, Joshua C. Cyktor, Joseph J. Eron, John W. Mellors, Colin Kovacs, Erika Benko, Alberto Bosque, R. Brad JonesList of authors in order
- Landing page
-
https://doi.org/10.1172/jci.insight.169028Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1172/jci.insight.169028Direct OA link when available
- Concepts
-
Granzyme B, Ex vivo, Cytotoxic T cell, Immunology, T cell, CD8, In vivo, Cancer research, Chemistry, Biology, Immune system, Cell biology, In vitro, Biochemistry, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
11Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 3, 2024: 4, 2023: 4Per-year citation counts (last 5 years)
- References (count)
-
73Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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