Lars Jørgen Østergaard

HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal. / Wu, Guoxin; Swanson, Michael; Talla, Aarthi; Graham, Donald; Strizki, Julie; Gorman, Daniel; Barnard, Richard Jo; Blair, Wade; Søgaard, Ole S; Tolstrup, Martin; Østergaard, Lars; Rasmussen, Thomas A; Sekaly, Rafick-Pierre; Archin, Nancie M; Margolis, David M; Hazuda, Daria J; Howell, Bonnie J.

In: JCI Insight, Vol. 2, No. 16, e92901, 17.08.2017.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Wu, G, Swanson, M, Talla, A, Graham, D, Strizki, J, Gorman, D, Barnard, RJ, Blair, W, Søgaard, OS, Tolstrup, M, Østergaard, L, Rasmussen, TA, Sekaly, R-P, Archin, NM, Margolis, DM, Hazuda, DJ & Howell, BJ 2017, 'HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal', JCI Insight, vol. 2, no. 16, e92901. https://doi.org/10.1172/jci.insight.92901

APA

Wu, G., Swanson, M., Talla, A., Graham, D., Strizki, J., Gorman, D., Barnard, R. J., Blair, W., Søgaard, O. S., Tolstrup, M., Østergaard, L., Rasmussen, T. A., Sekaly, R-P., Archin, N. M., Margolis, D. M., Hazuda, D. J., & Howell, B. J. (2017). HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal. JCI Insight, 2(16), [e92901]. https://doi.org/10.1172/jci.insight.92901

CBE

Wu G, Swanson M, Talla A, Graham D, Strizki J, Gorman D, Barnard RJ, Blair W, Søgaard OS, Tolstrup M, Østergaard L, Rasmussen TA, Sekaly R-P, Archin NM, Margolis DM, Hazuda DJ, Howell BJ. 2017. HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal. JCI Insight. 2(16):Article e92901. https://doi.org/10.1172/jci.insight.92901

MLA

Vancouver

Wu G, Swanson M, Talla A, Graham D, Strizki J, Gorman D et al. HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal. JCI Insight. 2017 Aug 17;2(16). e92901. https://doi.org/10.1172/jci.insight.92901

Author

Wu, Guoxin ; Swanson, Michael ; Talla, Aarthi ; Graham, Donald ; Strizki, Julie ; Gorman, Daniel ; Barnard, Richard Jo ; Blair, Wade ; Søgaard, Ole S ; Tolstrup, Martin ; Østergaard, Lars ; Rasmussen, Thomas A ; Sekaly, Rafick-Pierre ; Archin, Nancie M ; Margolis, David M ; Hazuda, Daria J ; Howell, Bonnie J. / HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal. In: JCI Insight. 2017 ; Vol. 2, No. 16.

Bibtex

@article{204f8c6faa0e47f68475de48fd0e8494,
title = "HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal",
abstract = "Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs. Importantly, we demonstrate that clinical administration of histone deacetylase inhibitors (HDACis; vorinostat and panobinostat) induced HIV gag p24, and ex vivo stimulation produced sufficient viral antigen to elicit immune-mediated cell killing using anti-gp120/CD3 bispecific antibody. These findings extend beyond classical nucleic acid endpoints, which are confounded by the predominance of mutated, defective proviruses and, of paramount importance, enable assessment of cells making HIV protein that can now be targeted by immunological approaches.",
keywords = "Journal Article",
author = "Guoxin Wu and Michael Swanson and Aarthi Talla and Donald Graham and Julie Strizki and Daniel Gorman and Barnard, {Richard Jo} and Wade Blair and S{\o}gaard, {Ole S} and Martin Tolstrup and Lars {\O}stergaard and Rasmussen, {Thomas A} and Rafick-Pierre Sekaly and Archin, {Nancie M} and Margolis, {David M} and Hazuda, {Daria J} and Howell, {Bonnie J}",
year = "2017",
month = aug,
day = "17",
doi = "10.1172/jci.insight.92901",
language = "English",
volume = "2",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "American Society for Clinical Investigation",
number = "16",

}

RIS

TY - JOUR

T1 - HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal

AU - Wu, Guoxin

AU - Swanson, Michael

AU - Talla, Aarthi

AU - Graham, Donald

AU - Strizki, Julie

AU - Gorman, Daniel

AU - Barnard, Richard Jo

AU - Blair, Wade

AU - Søgaard, Ole S

AU - Tolstrup, Martin

AU - Østergaard, Lars

AU - Rasmussen, Thomas A

AU - Sekaly, Rafick-Pierre

AU - Archin, Nancie M

AU - Margolis, David M

AU - Hazuda, Daria J

AU - Howell, Bonnie J

PY - 2017/8/17

Y1 - 2017/8/17

N2 - Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs. Importantly, we demonstrate that clinical administration of histone deacetylase inhibitors (HDACis; vorinostat and panobinostat) induced HIV gag p24, and ex vivo stimulation produced sufficient viral antigen to elicit immune-mediated cell killing using anti-gp120/CD3 bispecific antibody. These findings extend beyond classical nucleic acid endpoints, which are confounded by the predominance of mutated, defective proviruses and, of paramount importance, enable assessment of cells making HIV protein that can now be targeted by immunological approaches.

AB - Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs. Importantly, we demonstrate that clinical administration of histone deacetylase inhibitors (HDACis; vorinostat and panobinostat) induced HIV gag p24, and ex vivo stimulation produced sufficient viral antigen to elicit immune-mediated cell killing using anti-gp120/CD3 bispecific antibody. These findings extend beyond classical nucleic acid endpoints, which are confounded by the predominance of mutated, defective proviruses and, of paramount importance, enable assessment of cells making HIV protein that can now be targeted by immunological approaches.

KW - Journal Article

U2 - 10.1172/jci.insight.92901

DO - 10.1172/jci.insight.92901

M3 - Journal article

C2 - 28814661

VL - 2

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 16

M1 - e92901

ER -