A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection

Ines Frank, Arpan Acharya, Nanda K. Routhu, Meropi Aravantinou, Justin L. Harper, Stephanie Maldonado, Maria Sole Cigoli, Stanka Semova, Svetlana Mazel, Mirko Paiardini, Nina Derby, Siddappa N. Byrareddy, Elena Martinelli

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The establishment of latent infection and poorly characterized viral reservoirs in tissues represent major obstacles to a definitive cure for HIV. Non-human primate (NHP) models of HIV infection are critical to elucidate pathogenic processes and an essential tool to test novel therapeutic strategies. Thus, the availability of novel assays to measure residual viral replication and reservoirs in NHP models may increase their utility in the search for an HIV cure. We developed a tat/rev induced limiting dilution assay to measure the frequency of CD4+ T cells that express multiply-spliced(ms)_SIV RNA in presence and absence of stimulation. We validated the assay using cell lines and cells from blood and lymph nodes of SIV infected macaques. In vitro, SIV/SHIV TILDA detects only cells expressing viral proteins. In SIV/SHIV-infected macaques, CD4+ T cells that express msSIV/SHIV RNA (TILDA data) were detected also in the setting of very low/undetectable viremia. TILDA data were significantly higher after stimulation and correlated with plasma viral load (pVL). Interestingly, TILDA data from early cART initiation correlated with peak and AUC pVL post-cART interruption. In summary, we developed an assay that may be useful in characterizing viral reservoirs and determining the effect of HIV interventions in NHP models.

Original languageEnglish (US)
Article number12078
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Primates
HIV Infections
HIV
Macaca
Viral Load
RNA
T-Lymphocytes
Viremia
Viral Proteins
Area Under Curve
Blood Cells
Lymph Nodes
Cell Line
Infection
Therapeutics
In Vitro Techniques

ASJC Scopus subject areas

  • General

Cite this

Frank, I., Acharya, A., Routhu, N. K., Aravantinou, M., Harper, J. L., Maldonado, S., ... Martinelli, E. (2019). A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection. Scientific reports, 9(1), [12078]. https://doi.org/10.1038/s41598-019-48354-3

A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection. / Frank, Ines; Acharya, Arpan; Routhu, Nanda K.; Aravantinou, Meropi; Harper, Justin L.; Maldonado, Stephanie; Sole Cigoli, Maria; Semova, Stanka; Mazel, Svetlana; Paiardini, Mirko; Derby, Nina; Byrareddy, Siddappa N.; Martinelli, Elena.

In: Scientific reports, Vol. 9, No. 1, 12078, 01.12.2019.

Research output: Contribution to journalArticle

Frank, I, Acharya, A, Routhu, NK, Aravantinou, M, Harper, JL, Maldonado, S, Sole Cigoli, M, Semova, S, Mazel, S, Paiardini, M, Derby, N, Byrareddy, SN & Martinelli, E 2019, 'A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection', Scientific reports, vol. 9, no. 1, 12078. https://doi.org/10.1038/s41598-019-48354-3
Frank, Ines ; Acharya, Arpan ; Routhu, Nanda K. ; Aravantinou, Meropi ; Harper, Justin L. ; Maldonado, Stephanie ; Sole Cigoli, Maria ; Semova, Stanka ; Mazel, Svetlana ; Paiardini, Mirko ; Derby, Nina ; Byrareddy, Siddappa N. ; Martinelli, Elena. / A Tat/Rev Induced Limiting Dilution Assay to Measure Viral Reservoirs in Non-Human Primate Models of HIV Infection. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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