Pre-infection transcript levels of FAM26F in peripheral blood mononuclear cells inform about overall plasma viral load in acute and post-acute phase after simian immunodeficiency virus infection
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Medientyp:
E-Artikel
Titel:
Pre-infection transcript levels of FAM26F in peripheral blood mononuclear cells inform about overall plasma viral load in acute and post-acute phase after simian immunodeficiency virus infection
Beschreibung:
<jats:p>CD8<jats:sup>+</jats:sup> cells from simian immunodeficiency virus (SIV)-infected long-term non-progressors and some uninfected macaques can suppress viral replication <jats:italic>in vitro</jats:italic> without killing the infected cells. The aim of this study was to identify factors responsible for non-cytolytic viral suppression by transcriptional profiling and to investigate their potential impact on SIV replication. Results of microarray experiments and further validation with cells from infected and uninfected macaques revealed that <jats:italic>FAM26F</jats:italic> RNA levels distinguished CD8<jats:sup>+</jats:sup> cells of controllers and non-controllers (<jats:italic>P</jats:italic>=0.001). However, <jats:italic>FAM26F</jats:italic> was also expressed in CD4<jats:sup>+</jats:sup> T-cells and B-cells. <jats:italic>FAM26F</jats:italic> expression increased in lymphocytes after <jats:italic>in vitro</jats:italic> IFN-γ treatment on average 40-fold, and <jats:italic>ex vivo FAM26F</jats:italic> RNA levels in peripheral blood mononuclear cells correlated with plasma IFN-γ but not with IFN-α. Baseline <jats:italic>FAM26F</jats:italic> expression appeared to be stable for months, albeit the individual expression levels varied up to tenfold. Investigating its role in SIV-infection revealed that <jats:italic>FAM26F</jats:italic> was upregulated after infection (<jats:italic>P</jats:italic><0.0008), but did not directly correlate with viral load in contrast to <jats:italic>MX1</jats:italic> and <jats:italic>CXCL10</jats:italic>. However, pre-infection levels of <jats:italic>FAM26F</jats:italic> correlated inversely with overall plasma viral load (AUC) during the acute and post-acute phases of infection (e.g. AUC weeks post infection 0–8; no AIDS vaccine: <jats:italic>P</jats:italic><0.0001, Spearman rank correlation coefficient (rs)=−0.89, <jats:italic>n</jats:italic>=16; immunized with an AIDS vaccine: <jats:italic>P</jats:italic>=0.033, rs=−0.43; <jats:italic>n</jats:italic>=25). <jats:italic>FAM26F</jats:italic> transcript levels prior to infection can provide information about the pace and strength of the antiviral immune response during the early stage of infection. <jats:italic>FAM26F</jats:italic> expression represented, in our experiments, one of the earliest prognostic markers, and could supplement major histocompatibility complex (MHC)-typing to predict disease progression before SIV-infection.</jats:p>