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Research
Thomas Vollbrecht
University of California San Diego
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1151-8844
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
A reservoir of replication-competent but latent virus is the main obstacle to a cure for HIV-infection. Much of this reservoir resides in memory CD4 T cells. We hypothesized that these cells can be reactivated with antigens from HIV and other common pathogens to reverse latency.
Results
We obtained mononuclear cells from the peripheral blood of antiretroviral-treated patients with suppressed viremia. We tested pools of peptides and proteins derived from HIV and from other pathogens including CMV for their ability to reverse latency ex vivo by activation of memory responses. We assessed activation of the CD4 T cells by measuring the up-regulation of cell-surface CD69. We assessed HIV-expression using two assays: a real-time PCR assay for virion-associated viral RNA and a droplet digital PCR assay for cell-associated, multiply spliced viral mRNA. Reversal of latency occurred in a minority of cells from some participants, but no single antigen induced HIV-expression ex vivo consistently. When reversal of latency was induced by a specific peptide pool or protein, the extent was proportionally greater than that of T cell activation.
Conclusions
In this group of patients in whom antiretroviral therapy was started during chronic infection, the latent reservoir does not appear to consistently reside in CD4 T cells of a predominant antigen-specificity. Peptide-antigens reversed HIV-latency ex vivo with modest and variable activity. When latency was reversed by specific peptides or proteins, it was proportionally greater than the extent of T cell activation, suggesting partial enrichment of the latent reservoir in cells of specific antigen-reactivity.
Keywords
latency, HIV-1, antigen, CD4 T cell
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Peer Review Timeline
CURRENT STATUS: Published
View the published article at Retrovirology.
No community comments so far
Editorial decision: Accept
On 11 Nov, 2020
Review #1 received
Received 05 Nov, 2020
Reviewer #1 agreed
On 26 Oct, 2020
Editor assigned
On 21 Oct, 2020
Reviewers invited
Invitations sent on 21 Oct, 2020
Submission checks complete
On 20 Oct, 2020
Editor invited
On 20 Oct, 2020
Version 1
Posted 16 Jun, 2020
No comments provided
Editorial decision: Major revision
On 11 Aug, 2020
Review #2 received
Received 31 Jul, 2020
Review #1 received
Received 28 Jul, 2020
Reviewer #2 agreed
On 16 Jul, 2020
Reviewer #1 agreed
On 12 Jul, 2020
Reviewers invited
Invitations sent on 18 Jun, 2020
Editor assigned
On 13 Jun, 2020
First submitted
On 12 Jun, 2020
Submission checks complete
On 12 Jun, 2020
Editor invited
On 12 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Virology
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at Retrovirology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Thomas Vollbrecht
University of California San Diego
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1151-8844
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Retrovirology.
No community comments so far
Editorial decision: Accept
On 11 Nov, 2020
Review #1 received
Received 05 Nov, 2020
Reviewer #1 agreed
On 26 Oct, 2020
Editor assigned
On 21 Oct, 2020
Reviewers invited
Invitations sent on 21 Oct, 2020
Submission checks complete
On 20 Oct, 2020
Editor invited
On 20 Oct, 2020
Version 1
Posted 16 Jun, 2020
No comments provided
Editorial decision: Major revision
On 11 Aug, 2020
Review #2 received
Received 31 Jul, 2020
Review #1 received
Received 28 Jul, 2020
Reviewer #2 agreed
On 16 Jul, 2020
Reviewer #1 agreed
On 12 Jul, 2020
Reviewers invited
Invitations sent on 18 Jun, 2020
Editor assigned
On 13 Jun, 2020
First submitted
On 12 Jun, 2020
Submission checks complete
On 12 Jun, 2020
Editor invited
On 12 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Virology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Retrovirology.
Background
A reservoir of replication-competent but latent virus is the main obstacle to a cure for HIV-infection. Much of this reservoir resides in memory CD4 T cells. We hypothesized that these cells can be reactivated with antigens from HIV and other common pathogens to reverse latency.
Results
We obtained mononuclear cells from the peripheral blood of antiretroviral-treated patients with suppressed viremia. We tested pools of peptides and proteins derived from HIV and from other pathogens including CMV for their ability to reverse latency ex vivo by activation of memory responses. We assessed activation of the CD4 T cells by measuring the up-regulation of cell-surface CD69. We assessed HIV-expression using two assays: a real-time PCR assay for virion-associated viral RNA and a droplet digital PCR assay for cell-associated, multiply spliced viral mRNA. Reversal of latency occurred in a minority of cells from some participants, but no single antigen induced HIV-expression ex vivo consistently. When reversal of latency was induced by a specific peptide pool or protein, the extent was proportionally greater than that of T cell activation.
Conclusions
In this group of patients in whom antiretroviral therapy was started during chronic infection, the latent reservoir does not appear to consistently reside in CD4 T cells of a predominant antigen-specificity. Peptide-antigens reversed HIV-latency ex vivo with modest and variable activity. When latency was reversed by specific peptides or proteins, it was proportionally greater than the extent of T cell activation, suggesting partial enrichment of the latent reservoir in cells of specific antigen-reactivity.
Figure 1
Figure 2
Figure 3
Figure 4
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