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Viral protein Nef is detected in plasma of half of HIV-infected adults with undetectable plasma HIV RNA
ID
Ferdin, Jana
(
Author
),
ID
Goričar, Katja
(
Author
),
ID
Dolžan, Vita
(
Author
),
ID
Plemenitaš, Ana
(
Author
),
ID
Martin, Jeffrey
(
Author
),
ID
Peterlin, Matija Boris
(
Author
),
ID
Deeks, Steven G
(
Author
),
ID
Lenassi, Metka
(
Author
)
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https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191613
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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.
Language:
English
Keywords:
viral protein Nef
,
plasma
,
HIV
Work type:
Article
Typology:
1.01 - Original Scientific Article
Organization:
MF - Faculty of Medicine
Publication status:
Published
Publication version:
Version of Record
Year:
2018
Number of pages:
10 str.
Numbering:
Vol. 13, iss. 1, art. e0191613
PID:
20.500.12556/RUL-128738
UDC:
616.9
ISSN on article:
1932-6203
DOI:
10.1371/journal.pone.0191613
COBISS.SI-ID:
33608665
Publication date in RUL:
26.07.2021
Views:
918
Downloads:
179
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Record is a part of a journal
Title:
PloS one
Publisher:
PLOS
ISSN:
1932-6203
COBISS.SI-ID:
2005896
Licences
License:
CC BY 4.0, Creative Commons Attribution 4.0 International
Link:
http://creativecommons.org/licenses/by/4.0/
Description:
This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:
24.01.2018
Secondary language
Language:
Slovenian
Keywords:
virusni protein Nef
,
plazma
,
HIV
Projects
Funder:
ARRS - Slovenian Research Agency
Project number:
Z3-7198
Name:
Identifikacija in ovrednotenje novih biooznačevalcev za delno aktivne rezervoarje virusa HIV.
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-5499
Name:
Nef, izločen z eksosomi iz celic okuženih z virusom HIV, pomembno prispeva k razvoju nevroloških simptomov AIDS-a
Funder:
ARRS - Slovenian Research Agency
Project number:
P1-0170
Name:
Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku
Funder:
Other - Other funder or multiple funders
Funding programme:
UCSF/Gladstone Institute of Virology & Immunology CFAR
Project number:
P30 AI027763
Funder:
Other - Other funder or multiple funders
Funding programme:
CFAR Network of Integrated Systems
Project number:
R24 AI067039
Funder:
Other - Other funder or multiple funders
Funding programme:
Delaney AIDS Research Enterprise
Project number:
AI096109
Funder:
Other - Other funder or multiple funders
Funding programme:
Delaney AIDS Research Enterprise
Project number:
A127966
Funder:
Other - Other funder or multiple funders
Funding programme:
amfAR Institute for HIV Cure Research
Project number:
amfAR 109301
Funder:
NIH - National Institutes of Health
Project number:
R01 AI49104
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