Acute-Phase Response Proteins Are Overexpressed in Vaginal Mucosa and Plasma of HIV-Resistant Women upon Viral Challenge
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Date
2013Author
Burgener, A
Keynan, Y
Meyers, A
Birse, K
Abou, M
Westmacott, G
Kimani, J
Plummer, F
Fowke, K
Ball, T
Language
enMetadata
Show full item recordAbstract
Background: The primary receptive portals of entry for HIV are
through mucosal surfaces. Our previous studies show that HIVexposed
uninfected individuals (HESN) have unique innate responses
associated with resistance to HIV infection, including
increased anti-viral antiprotease expression coupled with a reduced
immune activation phenotype. However, we do not know
whether this immune state is static or induced upon viral exposure.
To answer this question we challenged HESN women with a
live attenuated Flumist vaccine and analyzed their mucosal and
systemic immune responses using a systems biology approach.
Methods: HESN women (n = 10) and HIV-susceptible controls
(n = 10) were challenged with an intranasal Flumist vaccine, and
clinical samples (cervicovaginal lavage (CVL), plasma) were
collected at Day 0, 1, 7 post-challenge. Mucosal/plasma were
analyzed by a combination of label-free tandem mass spectrometry,
hierarchical clustering, and pathway analysis.
Results: HESN women exhibited significant changes both mucosally
and systemically upon vaccine challenge 1 and 7 days
post-exposure. Of the > 450 proteins identified in CVL, 62 were
overexpressed (p < 0.05), and 48 overexpressed in plasma (of 220
proteins) (p < 0.05), over that of controls. Expression profiles
showed significant correlations between compartments. Hierarchical
clustering identified two major functional pathways
distinguishing HESN individuals, including the acute phase
and LXR-RXR response pathways (p < 1 · 10–17). Many of these
factors include antiproteases (serpins), apolipoproteins, complement
components, and SAA proteins which have known inhibitory
properties against HIV.
Conclusion: As the acute phase response pathway has been implicated
as important for controlling inflammation and early
stage viremia in HIV-infected individuals, overexpression of this
pathway supports the hypothesis that these factors are contributing
to reduced susceptibility to infection. Understanding the
role of these pathways in mucosal susceptibility to HIV may help
guide existing microbicide/vaccine strategies against HIV.
Citation
Burgener, A.,Keynan, Y.,Meyers, A .,Birse, K.,Abou, M.,Westmacott, G., Kimani, J .,Plummer, F.,Fowke, K ., Ball, T.,2013.Acute-Phase Response Proteins Are Overexpressed in Vaginal Mucosa and Plasma of HIV-Resistant Women upon Viral Challenge.Publisher
University of Nairobi
Collections
- Faculty of Health Sciences (FHS) [10385]