A murine viral outgrowth assay to detect residual HIV type 1 in patients with undetectable viral loads

Kelly Pate, Christopher W. Pohlmeyer, Victoria E. Walker-Sperling, Jeremy B. Foote, Kevin M. Najarro, Catherine G. Cryer, Maria Salgado, Lucio Gama, Elizabeth L. Engle, Erin N. Shirk, Suzanne E. Queen, Stanley Chioma, Meghan S. Vermillion, Brandon Bullock, Ming Li, Claire E. Lyons, Robert John Adams, Mary Christine Zink, Janice E Clements, Joseph L MankowskiJoel N Blankson

Research output: Contribution to journalArticle

Abstract

Background.Sensitive assays are needed for detection of residual human immunodeficiency virus (HIV) in patients with undetectable plasma viral loads to determine whether eradication strategies are effective. The gold standard quantitative viral outgrowth assay (QVOA) underestimates the magnitude of the viral reservoir. We sought to determine whether xenograft of leukocytes from HIV type 1 (HIV)-infected patients with undetectable plasma viral loads into immunocompromised mice would result in viral amplification. Methods.Peripheral blood mononuclear cells or purified CD4+ T cells from HIV or simian immunodeficiency virus (SIV)-infected subjects with undetectable plasma viral loads were adoptively transferred into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. The mice were monitored for viremia following depletion of human CD8+ T cells to minimize antiviral activity. In some cases, humanized mice were also treated with activating anti-CD3 antibody. Results.With this murine viral outgrowth assay (MVOA), we successfully amplified replication-competent HIV or SIV from all subjects tested, including 5 HIV-positive patients receiving suppressive antiretroviral therapy (ART) and 6 elite controllers or suppressors who were maintaining undetectable viral loads without ART, including an elite suppressor from whom we were unable to recover virus by QVOA. Conclusions.Our results suggest that the MVOA has the potential to serve as a powerful tool to identify residual HIV in patients with undetectable viral loads.

Original languageEnglish (US)
Pages (from-to)1387-1396
Number of pages10
JournalJournal of Infectious Diseases
Volume212
Issue number9
DOIs
StatePublished - Nov 1 2015

Fingerprint

Viral Load
HIV-1
HIV
Simian Immunodeficiency Virus
T-Lymphocytes
Viremia
Heterografts
Antiviral Agents
Anti-Idiotypic Antibodies
Blood Cells
Leukocytes
Viruses
Therapeutics

Keywords

  • cure
  • HIV
  • humanized mouse
  • quantitative viral outgrowth assay (QVOA)
  • SIV

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

A murine viral outgrowth assay to detect residual HIV type 1 in patients with undetectable viral loads. / Pate, Kelly; Pohlmeyer, Christopher W.; Walker-Sperling, Victoria E.; Foote, Jeremy B.; Najarro, Kevin M.; Cryer, Catherine G.; Salgado, Maria; Gama, Lucio; Engle, Elizabeth L.; Shirk, Erin N.; Queen, Suzanne E.; Chioma, Stanley; Vermillion, Meghan S.; Bullock, Brandon; Li, Ming; Lyons, Claire E.; Adams, Robert John; Zink, Mary Christine; Clements, Janice E; Mankowski, Joseph L; Blankson, Joel N.

In: Journal of Infectious Diseases, Vol. 212, No. 9, 01.11.2015, p. 1387-1396.

Research output: Contribution to journalArticle

Pate, K, Pohlmeyer, CW, Walker-Sperling, VE, Foote, JB, Najarro, KM, Cryer, CG, Salgado, M, Gama, L, Engle, EL, Shirk, EN, Queen, SE, Chioma, S, Vermillion, MS, Bullock, B, Li, M, Lyons, CE, Adams, RJ, Zink, MC, Clements, JE, Mankowski, JL & Blankson, JN 2015, 'A murine viral outgrowth assay to detect residual HIV type 1 in patients with undetectable viral loads', Journal of Infectious Diseases, vol. 212, no. 9, pp. 1387-1396. https://doi.org/10.1093/infdis/jiv230
Pate, Kelly ; Pohlmeyer, Christopher W. ; Walker-Sperling, Victoria E. ; Foote, Jeremy B. ; Najarro, Kevin M. ; Cryer, Catherine G. ; Salgado, Maria ; Gama, Lucio ; Engle, Elizabeth L. ; Shirk, Erin N. ; Queen, Suzanne E. ; Chioma, Stanley ; Vermillion, Meghan S. ; Bullock, Brandon ; Li, Ming ; Lyons, Claire E. ; Adams, Robert John ; Zink, Mary Christine ; Clements, Janice E ; Mankowski, Joseph L ; Blankson, Joel N. / A murine viral outgrowth assay to detect residual HIV type 1 in patients with undetectable viral loads. In: Journal of Infectious Diseases. 2015 ; Vol. 212, No. 9. pp. 1387-1396.
@article{94e5cfbd27e14d708e68b8977cbda457,
title = "A murine viral outgrowth assay to detect residual HIV type 1 in patients with undetectable viral loads",
abstract = "Background.Sensitive assays are needed for detection of residual human immunodeficiency virus (HIV) in patients with undetectable plasma viral loads to determine whether eradication strategies are effective. The gold standard quantitative viral outgrowth assay (QVOA) underestimates the magnitude of the viral reservoir. We sought to determine whether xenograft of leukocytes from HIV type 1 (HIV)-infected patients with undetectable plasma viral loads into immunocompromised mice would result in viral amplification. Methods.Peripheral blood mononuclear cells or purified CD4+ T cells from HIV or simian immunodeficiency virus (SIV)-infected subjects with undetectable plasma viral loads were adoptively transferred into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. The mice were monitored for viremia following depletion of human CD8+ T cells to minimize antiviral activity. In some cases, humanized mice were also treated with activating anti-CD3 antibody. Results.With this murine viral outgrowth assay (MVOA), we successfully amplified replication-competent HIV or SIV from all subjects tested, including 5 HIV-positive patients receiving suppressive antiretroviral therapy (ART) and 6 elite controllers or suppressors who were maintaining undetectable viral loads without ART, including an elite suppressor from whom we were unable to recover virus by QVOA. Conclusions.Our results suggest that the MVOA has the potential to serve as a powerful tool to identify residual HIV in patients with undetectable viral loads.",
keywords = "cure, HIV, humanized mouse, quantitative viral outgrowth assay (QVOA), SIV",
author = "Kelly Pate and Pohlmeyer, {Christopher W.} and Walker-Sperling, {Victoria E.} and Foote, {Jeremy B.} and Najarro, {Kevin M.} and Cryer, {Catherine G.} and Maria Salgado and Lucio Gama and Engle, {Elizabeth L.} and Shirk, {Erin N.} and Queen, {Suzanne E.} and Stanley Chioma and Vermillion, {Meghan S.} and Brandon Bullock and Ming Li and Lyons, {Claire E.} and Adams, {Robert John} and Zink, {Mary Christine} and Clements, {Janice E} and Mankowski, {Joseph L} and Blankson, {Joel N}",
year = "2015",
month = "11",
day = "1",
doi = "10.1093/infdis/jiv230",
language = "English (US)",
volume = "212",
pages = "1387--1396",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - A murine viral outgrowth assay to detect residual HIV type 1 in patients with undetectable viral loads

AU - Pate, Kelly

AU - Pohlmeyer, Christopher W.

AU - Walker-Sperling, Victoria E.

AU - Foote, Jeremy B.

AU - Najarro, Kevin M.

AU - Cryer, Catherine G.

AU - Salgado, Maria

AU - Gama, Lucio

AU - Engle, Elizabeth L.

AU - Shirk, Erin N.

AU - Queen, Suzanne E.

AU - Chioma, Stanley

AU - Vermillion, Meghan S.

AU - Bullock, Brandon

AU - Li, Ming

AU - Lyons, Claire E.

AU - Adams, Robert John

AU - Zink, Mary Christine

AU - Clements, Janice E

AU - Mankowski, Joseph L

AU - Blankson, Joel N

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Background.Sensitive assays are needed for detection of residual human immunodeficiency virus (HIV) in patients with undetectable plasma viral loads to determine whether eradication strategies are effective. The gold standard quantitative viral outgrowth assay (QVOA) underestimates the magnitude of the viral reservoir. We sought to determine whether xenograft of leukocytes from HIV type 1 (HIV)-infected patients with undetectable plasma viral loads into immunocompromised mice would result in viral amplification. Methods.Peripheral blood mononuclear cells or purified CD4+ T cells from HIV or simian immunodeficiency virus (SIV)-infected subjects with undetectable plasma viral loads were adoptively transferred into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. The mice were monitored for viremia following depletion of human CD8+ T cells to minimize antiviral activity. In some cases, humanized mice were also treated with activating anti-CD3 antibody. Results.With this murine viral outgrowth assay (MVOA), we successfully amplified replication-competent HIV or SIV from all subjects tested, including 5 HIV-positive patients receiving suppressive antiretroviral therapy (ART) and 6 elite controllers or suppressors who were maintaining undetectable viral loads without ART, including an elite suppressor from whom we were unable to recover virus by QVOA. Conclusions.Our results suggest that the MVOA has the potential to serve as a powerful tool to identify residual HIV in patients with undetectable viral loads.

AB - Background.Sensitive assays are needed for detection of residual human immunodeficiency virus (HIV) in patients with undetectable plasma viral loads to determine whether eradication strategies are effective. The gold standard quantitative viral outgrowth assay (QVOA) underestimates the magnitude of the viral reservoir. We sought to determine whether xenograft of leukocytes from HIV type 1 (HIV)-infected patients with undetectable plasma viral loads into immunocompromised mice would result in viral amplification. Methods.Peripheral blood mononuclear cells or purified CD4+ T cells from HIV or simian immunodeficiency virus (SIV)-infected subjects with undetectable plasma viral loads were adoptively transferred into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. The mice were monitored for viremia following depletion of human CD8+ T cells to minimize antiviral activity. In some cases, humanized mice were also treated with activating anti-CD3 antibody. Results.With this murine viral outgrowth assay (MVOA), we successfully amplified replication-competent HIV or SIV from all subjects tested, including 5 HIV-positive patients receiving suppressive antiretroviral therapy (ART) and 6 elite controllers or suppressors who were maintaining undetectable viral loads without ART, including an elite suppressor from whom we were unable to recover virus by QVOA. Conclusions.Our results suggest that the MVOA has the potential to serve as a powerful tool to identify residual HIV in patients with undetectable viral loads.

KW - cure

KW - HIV

KW - humanized mouse

KW - quantitative viral outgrowth assay (QVOA)

KW - SIV

UR - http://www.scopus.com/inward/record.url?scp=84946147894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946147894&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiv230

DO - 10.1093/infdis/jiv230

M3 - Article

C2 - 25883388

AN - SCOPUS:84946147894

VL - 212

SP - 1387

EP - 1396

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 9

ER -