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Predictive value of microRNAs for decreasing CD4 T cell count among HIV-1- infected patients who spontaneously control viral replication (HIV controllers)
4th International Conference on Medical Microbiology
May 20-21, 2019 | Vienna, Austria
Alejandro Vallejo
Ramón y Cajal University Hospital, Spain
Posters & Accepted Abstracts : Microbiol Curr Res
Abstract:
Background: A small group of HIV-1-infected individuals
(5-15%) control disease progression for several years in the
absence of any antiretroviral therapy. Among this group, elite
controllers spontaneously control HIV-1 replication (below 50
HIV-1 RNA copies/ml); nevertheless, they are still susceptible
to have several aspects of the immune response deregulated,
especially elevated immune activation and inflammation.
Homeostatic factors contribute to maintain a stable pool of
T cells in this situation where T cell apoptosis is enhanced.
This situation promotes the release of micro vesicles, such
as exosomes that are released by the cells and are present
in blood, urine and saliva. This content includes miRNAs,
small non-coding RNA capable of recognizing specific mRNA
and inhibiting its translation into proteins. These molecules
may thus promote hematopoietic stem cells and regulate
the immune system and inflammatory processes that
could influence the homeostasis cell equilibrium. HIV could
interfere with the exosomal pathway. The direct influence of
exosomal miRNAs on the cells of the immune system during
HIV infection is a topic that is still poorly understood. Since
exosomes can modulate immune responses and may affect
HIV pathogenesis, we conducted this cross-sectional study of
quantification of selected miRNAs in HIV elite controllers. We
also investigated the association of plasma-derived exosome
miRNA levels with both soluble cytokine levels and cellular
immune activation.
Methods: Two groups of elite controllers were analysed,
i.e., those that during the follow up had stable or increasing
CD4 T cell count (SEC, N=21), and those who had significant
decline of CD4 T cell count (DEC, N=11). Plasma-derived
exosomes were used to determine the expression of miRs
and determine their association to soluble cytokine markers
and cellular immune activation.
Results: Plasma exosome-derived miR-16 and miR-21 are
downregulated in DEC group, while miR-221 was upregulated
compared to SEC group. Only miR-21 was independently
associated with CD4 T cell decline in elite controllers (p=0.049;
odds ratio 0.369, IC95 [0.137-0.994]). On the other hand,
negative correlation between plasma exosome-derived miR-
21 and MCP-1 was found (p=0.020). No correlation between
expression of miRs and cellular immune activation markers
was found.
Conclusion: Exosome-derived miR-21 might be used as a
valuable prognosis soluble biomarker to define HIV-1 elite
controllers who will have significant decay in their CD4 T cell
counts.
Biography:
E-mail:
alejandro.vallejo@salud.madrid.orgPDF HTML