title: 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.
abstract: CD8+ cells from simian immunodeficiency virus (SIV)-infected long-term non-progressors and some uninfected macaques can suppress viral replication in vitro 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 FAM26F RNA levels distinguished CD8+ cells of controllers and non-controllers (P=0.001). However, FAM26F was also expressed in CD4+ T-cells and B-cells. FAM26F expression increased in lymphocytes after in vitro IFN-γ treatment on average 40-fold, and ex vivo FAM26F RNA levels in peripheral blood mononuclear cells correlated with plasma IFN-γ but not with IFN-α. Baseline FAM26F expression appeared to be stable for months, albeit the individual expression levels varied up to tenfold. Investigating its role in SIV-infection revealed that FAM26F was upregulated after infection (P<0.0008), but did not directly correlate with viral load in contrast to MX1 and CXCL10. However, pre-infection levels of FAM26F 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: P<0.0001, Spearman rank correlation coefficient (rs)=-0.89, n=16; immunized with an AIDS vaccine: P=0.033, rs=-0.43; n=25). FAM26F transcript levels prior to infection can provide information about the pace and strength of the antiviral immune response during the early stage of infection. FAM26F 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.
authors.affiliation: Deutsches Primatenzentrum GmbH, Leibniz-Institut für Primatenforschung, Unit of Infection Models, Göttingen, Germany.
authors.forename: Aneela
authors.initials: A
authors.lastname: Javed
authors.affiliation: Deutsches Primatenzentrum GmbH, Leibniz-Institut für Primatenforschung, Unit of Infection Models, Göttingen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Leuchte
authors.affiliation: Transcriptome and Genome Analysis Laboratory (TAL), Faculty of Medicine, University of Göttingen, Göttingen, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Salinas
authors.affiliation: Transcriptome and Genome Analysis Laboratory (TAL), Faculty of Medicine, University of Göttingen, Göttingen, Germany.
authors.forename: Lennart
authors.initials: L
authors.lastname: Opitz
authors.affiliation: Deutsches Primatenzentrum GmbH, Leibniz-Institut für Primatenforschung, Unit of Infection Models, Göttingen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Stahl-Hennig
authors.affiliation: Tumor Immunology Lab, Hematology and Oncology, Medical University Innsbruck and Tyrolean Cancer Research Institute, Innsbruck, Austria.
authors.forename: Sieghart
authors.initials: S
authors.lastname: Sopper
authors.affiliation: Deutsches Primatenzentrum GmbH, Leibniz-Institut für Primatenforschung, Unit of Infection Models, Göttingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Sauermann
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D004195:Disease Models, Animal; D015658:HIV Infections / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology*; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D008562:Membrane Glycoproteins; D012367:RNA, Viral; D007371:Interferon-gamma