Jana Ferdin (Author), Katja Goričar (Author), Vita Dolžan (Author), Ana Plemenitaš (Author), Jeffrey Martin (Author), Matija Boris Peterlin (Author), Steven G Deeks (Author), Metka Lenassi (Author)

Abstract

Objective To address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects. Design We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA) and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort. Methods This study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort). We optimized an ELISA for detection of plasma Nef in HIV-negative subjects and HIV-infected non-controllers, and evaluated its utility to quantify plasma Nef levels in a cross-sectional study of ART-suppressed and elite controller HIV-infected subjects. Results Here, we describe the performance of an optimized HIV Nef ELISA. When we applied this assay to the study cohort we found that plasma Nef levels were correlated with plasma HIV RNA levels in untreated disease. However, we were able to detect Nef in plasma of approximately half of subjects on ART or with elite control, despite the lack of detectable plasma HIV RNA levels using standard assays. Plasma Nef levels were not consistently associated with CD4+ T-cell count, CD8+ T-cell count, self-reported nadir CD4+ T-cell count or the CD4+/CD8+ T-cell ratio in HIV-infected subjects. Conclusion Since plasma HIV RNA levels are undetectable in virally suppressed subjects, it is reasonable to assume that viral protein expression in leaky reservoir, and not plasma virions, is the source of Nef accumulating in plasma. To examine this further, improvements of the assay sensitivity, by lowering the background through improvements in the quality of Nef antibodies, and detailed characterization of the HIV reservoirs are needed.

Keywords

viral protein Nef;plasma;HIV;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL MF - Faculty of Medicine
UDC: 616.9
COBISS: 33608665 Link will open in a new window
ISSN: 1932-6203
Views: 314
Downloads: 92
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Other data

Secondary language: Slovenian
Secondary keywords: virusni protein Nef;plazma;HIV;
Type (COBISS): Article
Pages: str. 1-10
Volume: ǂVol. ǂ13
Issue: ǂiss. ǂ1
Chronology: Jan. 2018
DOI: 10.1371/journal.pone.0191613
ID: 13177521