A Murine Viral Outgrowth Assay to Detect Residual HIV Type 1 in Patients With Undetectable Viral Loads
| Autor: | Meghan S. Vermillion, Kelly A. Metcalf Pate, Catherine G. Cryer, Maria Salgado, Ming Li, Janice E. Clements, Elizabeth L. Engle, Brandon T. Bullock, Joel N. Blankson, Robert J. Adams, Victoria E. Walker-Sperling, Jeremy B. Foote, M. Christine Zink, Lucio Gama, Suzanne E. Queen, Kevin Najarro, Erin N. Shirk, Christopher W. Pohlmeyer, Stanley Chioma, Joseph L. Mankowski, Claire E. Lyons |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male viruses Viremia HIV Infections CD8-Positive T-Lymphocytes medicine.disease_cause Peripheral blood mononuclear cell Virus Major Articles and Brief Reports Mice Antiretroviral Therapy Highly Active medicine Immunology and Allergy Animals Humans biology Simian immunodeficiency virus Viral Load medicine.disease Virology Disease Models Animal Infectious Diseases Humanized mouse Immunology biology.protein HIV-1 Leukocytes Mononuclear Interleukin-2 Macaca Simian Immunodeficiency Virus Antibody Viral load CD8 |
| Popis: | 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-Prkdc(scid)Il2rg(tm1Wjl)/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. |
| Databáze: | OpenAIRE |
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