Viral protein Nef is detected in plasma of half of HIV-infected adults with undetectable plasma HIV RNA
Year: 2018
Type: article
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.
Source: PLoS ONE
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: amfAR, The Foundation for AIDS Research, Delaney AIDS Research Enterprise, Javna Agencija za Raziskovalno Dejavnost RS, National Institutes of Health, University of California, San Francisco, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: G1245695584, HARC Center: HIV Accessory and Regulatory Complexes, G2428225874, Identification and evaluation of novel biomarkers for residual active HIV reservoirs., Nef, izločen z eksosomi iz celic okuženih z virusom HIV, pomembno prispeva k razvoju nevroloških simptomov AIDS-a (Slovene), G3181090803, DARE: Delaney AIDS Research Enterprise to find a cure., TAT Transactivation, Molecular mechanisms of regulation of cellular processes related to some human diseases, G6444951560, G6759634997, TAT Transactivation, G864826021, G9000078127, G9000271296, CFAR Network of Integrated Clinical Systems (CNICS), UCSF-Bay Area Center for AIDS Research
OpenAlex ID: W2784949616