Ultrasensitive HIV-1 p24 assay detects single infected cells and differences in reservoir induction by latency reversal agents

Journal of Virology

Volumn 91, Issue 6, 2017, Pages

  Passaes, Caroline Pereira Bittencourt ^a   Bruel, Timothée ^a,b   Decalf, Jérémie ^a,c   David, Annie ^a   Angin, Mathieu ^a   Monceaux, Valerie ^a   Muller Trutwin, Michaela ^a,b   Noel, Nicolas ^d,e,f   Bourdic, Katia ^f   Lambotte, Olivier ^d,e,f,n   Albert, Matthew L ^a,c,g   Duffy, Darragh ^a,g   Schwartz, Olivier ^a,b   Sáez Cirión, Asier ^a   Rouzioux, Christine ^h   Autran, Brigitte ⁱ   Benkirane, Monsef ^j   Guedj, Jeremie ^k   Hocqueloux, Laurent ^l   Katlama, Christine ^m   Legrand, Roger ^o   Meyer, Laurence ^p   Mouquet, Hugo ^a   Müller Trutwin, Michaela ^a   Taburet, Anne Marie ⁿ   Van Lint, Carine ^q   more..

^a INSTITUT PASTEUR   (France)

^b Vaccine Research Institute (VRI)   (France)

^c GENENTECH INC   (United States)

^d INSERM U1184   (France)

^e CEA   (France)

^f ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^g INSTITUT PASTEUR   (France)

^h HÔPITAL NECKER ENFANTS MALADES   (France)

ⁱ SORBONNE UNIVERSITÉ   (France)

^j INSTITUTE OF HUMAN GENETICS   (France)

^k BICHAT HOSPITAL   (France)

^l CENTRE HOSPITALIER RÉGIONAL D ORLÉANS   (France)

^m PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

ⁿ BICÊTRE HOSPITAL   (France)

^o INSTITUT DE RADIOPROTECTION ET DE SÛRETÉ NUCLÉAIRE   (France)

^p INSERM   (France)

^q UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

more..

Author keywords

CD4+ T cells; HIV cure; HIV reservoir; HIV 1; Latency reversal agents; P24; Single cell

Indexed keywords

ANTIRETROVIRUS AGENT; GAG PROTEIN; PHYTOHEMAGGLUTININ; PHYTOHEMAGGLUTININ L; PROSTRATIN; PROTEIN KINASE C ACTIVATOR; UNCLASSIFIED DRUG; VIRUS RNA;

ARTICLE; BIOCHEMICAL EQUIPMENT; CD4+ T LYMPHOCYTE; CELL SELECTION; CELL STIMULATION; CONTROLLED STUDY; DIGITAL ENZYME LINKED IMMUNOSORBENT ASSAY; DILUTION; DRUG EFFICACY; DRUG TARGETING; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW BASED SINGLE CELL SORTING; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; IMMUNOASSAY; NONHUMAN; PROTEIN ANALYSIS; PROTEIN SYNTHESIS; QUANTITATIVE ANALYSIS; RNA SYNTHESIS; SENSITIVITY ANALYSIS; SERIAL DILUTION; VIRUS CELL INTERACTION; VIRUS LATENCY; VIRUS REACTIVATION; COMPARATIVE STUDY; DRUG EFFECTS; EVALUATION STUDY; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; PHYSIOLOGY; PROCEDURES; SENSITIVITY AND SPECIFICITY; VIROLOGY; VIRUS ACTIVATION;

CD4-POSITIVE T-LYMPHOCYTES; HIV CORE PROTEIN P24; HIV INFECTIONS; HIV-1; HUMANS; SENSITIVITY AND SPECIFICITY; VIROLOGY; VIRUS ACTIVATION; VIRUS LATENCY;

EID: 85014081631     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.02296-16     Document Type: Article

References (30)

1. Chun TW, Justement JS, Murray D, Hallahan CW, Maenza J, Collier AC, Sheth PM, Kaul R, Ostrowski M, Moir S, Kovacs C, Fauci AS. 2010. Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication. AIDS 24:2803-2808. https://doi.org/10.1097/QAD. 0b013e328340a239.
2. Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS. 1997. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A 94:13193-13197. https://doi.org/10.1073/pnas.94.24.13193.
3. Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, Boucher G, Boulassel MR, Ghattas G, Brenchley JM, Schacker TW, Hill BJ, Douek DC, Routy JP, Haddad EK, Sekaly RP. 2009. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 15:893-900. https://doi.org/10.1038/nm.1972.
4. Fletcher CV, Staskus K, Wietgrefe SW, Rothenberger M, Reilly C, Chipman JG, Beilman GJ, Khoruts A, Thorkelson A, Schmidt TE, Anderson J, Perkey K, Stevenson M, Perelson AS, Douek DC, Haase AT, Schacker TW. 2014. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A 111: 2307-2312. https://doi.org/10.1073/pnas.1318249111.
5. Passaes CP, Saez-Cirion A. 2014. HIV cure research: advances and prospects. Virology 454-455:340-352. https://doi.org/10.1016/j.virol.2014.02.021.
6. Chun TW, Moir S, Fauci AS. 2015. HIV reservoirs as obstacles and opportunities for an HIV cure. Nat Immunol 16:584-589. https://doi.org/10.1038/ni.3152.
7. Deeks SG, Lewin SR, Ross AL, Ananworanich J, Benkirane M, Cannon P, Chomont N, Douek D, Lifson JD, Lo YR, Kuritzkes D, Margolis D, Mellors J, Persaud D, Tucker JD, Barre-Sinoussi F, International AIDS Society Towards a Cure Working Group, Alter G, Auerbach J, Autran B, Barouch DH, Behrens G, Cavazzana M, Chen Z, Cohen EA, Corbelli GM, Eholie S, Eyal N, Fidler S, Garcia L, Grossman C, Henderson G, Henrich TJ, Jefferys R, Kiem HP, McCune J, Moodley K, Newman PA, Nijhuis M, Nsubuga MS, Ott M, Palmer S, Richman D, Saez-Cirion A, Sharp M, Siliciano J, Silvestri G, Singh J, Spire B, Taylor J, et al. 2016. International AIDS Society global scientific strategy: towards an HIV cure 2016. Nat Med 22:839-850. https://doi.org/10.1038/nm.4108.
8. Rouzioux C, Melard A, Avettand-Fenoel V. 2014. Quantification of total HIV1-DNA in peripheral blood mononuclear cells. Methods Mol Biol 1087:261-270. https://doi.org/10.1007/978-1-62703-670-2_21.
9. O'Doherty U, Swiggard WJ, Jeyakumar D, McGain D, Malim MH. 2002. A sensitive, quantitative assay for human immunodeficiency virus type 1 integration. J Virol 76:10942-10950. https://doi.org/10.1128/JVI.76.21.10942-10950.2002.
10. Laird GM, Eisele EE, Rabi SA, Lai J, Chioma S, Blankson JN, Siliciano JD, Siliciano RF. 2013. Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay. PLoS Pathog 9:e1003398. https://doi.org/10.1371/journal.ppat.1003398.
11. + T-cells carrying replication-competent virus in HIV-1-infected individuals. Methods Mol Biol 304:3-15.
12. Procopio FA, Fromentin R, Kulpa DA, Brehm JH, Bebin AG, Strain MC, Richman DD, O'Doherty U, Palmer S, Hecht FM, Hoh R, Barnard RJ, Miller MD, Hazuda DJ, Deeks SG, Sekaly RP, Chomont N. 2015. A novel assay to measure the magnitude of the inducible viral reservoir in HIV-infected individuals. EBioMedicine 2:874-883. https://doi.org/10.1016/j.ebiom.2015.06.019.
13. Pasternak AO, Lukashov VV, Berkhout B. 2013. Cell-associated HIV RNA: a dynamic biomarker of viral persistence. Retrovirology 10:41. https://doi.org/10.1186/1742-4690-10-41.
14. Rissin DM, Fournier DR, Piech T, Kan CW, Campbell TG, Song L, Chang L, Rivnak AJ, Patel PP, Provuncher GK, Ferrell EP, Howes SC, Pink BA, Minnehan KA, Wilson DH, Duffy DC. 2011. Simultaneous detection of single molecules and singulated ensembles of molecules enables immunoassays with broad dynamic range. Anal Chem 83:2279-2285. https://doi.org/10.1021/ac103161b.
15. Rissin DM, Kan CW, Campbell TG, Howes SC, Fournier DR, Song L, Piech T, Patel PP, Chang L, Rivnak AJ, Ferrell EP, Randall JD, Provuncher GK, Walt DR, Duffy DC. 2010. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol 28:595-599. https://doi.org/10.1038/nbt.1641.
16. Kelley SO, Mirkin CA, Walt DR, Ismagilov RF, Toner M, Sargent EH. 2014. Advancing the speed, sensitivity and accuracy of biomolecular detection using multi-length-scale engineering. Nat Nanotechnol 9:969-980. https://doi.org/10.1038/nnano.2014.261.
17. Wilson DH, Rissin DM, Kan CW, Fournier DR, Piech T, Campbell TG, Meyer RE, Fishburn MW, Cabrera C, Patel PP, Frew E, Chen Y, Chang L, Ferrell EP, von Einem V, McGuigan W, Reinhardt M, Sayer H, Vielsack C, Duffy DC. 2016. The Simoa HD-1 analyzer: a novel fully automated digital immunoassay analyzer with single-molecule sensitivity and multiplexing. J Lab Autom 21:533-547. https://doi.org/10.1177/2211068215589580.
18. Cabrera C, Chang L, Stone M, Busch M, Wilson DH. 2015. Rapid, fully automated digital immunoassay for p24 Protein with the sensitivity of nucleic acid amplification for detecting acute HIV infection. Clin Chem 61:1372-1380. https://doi.org/10.1373/clinchem.2015.243287.
19. Bruel T, Guivel-Benhassine F, Amraoui S, Malbec M, Richard L, Bourdic K, Donahue DA, Lorin V, Casartelli N, Noel N, Lambotte O, Mouquet H, Schwartz O. 2016. Elimination of HIV-1-infected cells by broadly neutralizing antibodies. Nat Commun 7:10844. https://doi.org/10.1038/ncomms10844.
20. Noel N, Pena R, David A, Avettand-Fenoel V, Erkizia I, Jimenez E, Lecuroux C, Rouzioux C, Boufassa F, Pancino G, Venet A, Van Lint C, Martinez-Picado J, Lambotte O, Saez-Cirion A, Prado JG. 2016. Long-term spontaneous control of HIV-1 is related to low frequency of infected cells and inefficient viral reactivation. J Virol 90:6148-6158. https://doi.org/10.1128/JVI.00419-16.
21. Eriksson S, Graf EH, Dahl V, Strain MC, Yukl SA, Lysenko ES, Bosch RJ, Lai J, Chioma S, Emad F, Abdel-Mohsen M, Hoh R, Hecht F, Hunt P, Somsouk M, Wong J, Johnston R, Siliciano RF, Richman DD, O'Doherty U, Palmer S, Deeks SG, Siliciano JD. 2013. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog 9:e1003174. https://doi.org/10.1371/journal.ppat.1003174.
22. Yukl SA, Boritz E, Busch M, Bentsen C, Chun TW, Douek D, Eisele E, Haase A, Ho YC, Hutter G, Justement JS, Keating S, Lee TH, Li P, Murray D, Palmer S, Pilcher C, Pillai S, Price RW, Rothenberger M, Schacker T, Siliciano J, Siliciano R, Sinclair E, Strain M, Wong J, Richman D, Deeks SG. 2013. Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient. PLoS Pathog 9:e1003347. https://doi.org/10.1371/journal.ppat.1003347.
23. Bruner KM, Hosmane NN, Siliciano RF. 2015. Towards an HIV-1 cure: measuring the latent reservoir. Trends Microbiol 23:192-203. https://doi.org/10.1016/j.tim.2015.01.013.
24. Rouzioux C, Richman D. 2013. How to best measure HIV reservoirs? Curr Opin HIV AIDS 8:170-175. https://doi.org/10.1097/COH. 0b013e32835fc619.
25. Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DI, Lai J, Blankson JN, Siliciano JD, Siliciano RF. 2013. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155:540-551. https://doi.org/10.1016/j.cell.2013.09.020.
26. + T cells from patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A 111:7078-7083. https://doi.org/10.1073/pnas.1402873111.
27. Bullen CK, Laird GM, Durand CM, Siliciano JD, Siliciano RF. 2014. New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo. Nat Med 20:425-429. https://doi.org/10.1038/nm.3489.
28. Bouchat S, Delacourt N, Kula A, Darcis G, Van Driessche B, Corazza F, Gatot JS, Melard A, Vanhulle C, Kabeya K, Pardons M, Avettand-Fenoel V, Clumeck N, De Wit S, Rohr O, Rouzioux C, Van Lint C. 2015. Sequential treatment with 5-aza-2=-deoxycytidine and deacetylase inhibitors reactivates HIV-1. EMBO Mol Med 8:117-138.
29. + T-cells to recognition by cytotoxic t-lymphocytes. PLoS Pathog 12:e1005545. https://doi.org/10.1371/journal.ppat.1005545.
30. Korin YD, Brooks DG, Brown S, Korotzer A, Zack JA. 2002. Effects of prostratin on T-cell activation and human immunodeficiency virus latency. J Virol 76:8118-8123. https://doi.org/10.1128/JVI.76.16.8118-8123.2002.