Our study links the HIV/SIV infection-induced fatty acid enzyme ACSS2 to HIV latency and identifies histone lysine crotonylation as a novel epigenetic regulator for HIV transcription that can be targeted for HIV eradication.
Importantly, the addition of PH-797804 to ART initiated during chronic SIV infection reduced immune activation and restored immune system parameters to the levels observed when ART was initiated on week 1 after infection.
Importantly, the addition of PH-797804 to ART initiated during chronic SIV infection reduced immune activation and restored immune system parameters to the levels observed when ART was initiated on week 1 after infection.
We found a significant increase in caspase-1 and IL-18 in SIV infection that positively correlated with inflammatory monocytes and negatively correlated with CD4<sup>+</sup> T cell counts.
Furthermore, AFB1 promoted the polarization of SIV-infected PAMs to the M1 phenotype at 8 hpi and to the M2 phenotype at 24 hpi, as measured by the increases in IL-10 expression and in the number of CD206-positive PAMs as well as by the morphological changes observed by scanning electron microscopy.
Here we show that chronic simian immunodeficiency virus (SIV) infection is characterized by an expansion of either lymph node germinal center (GC) B cells that co-express Bcl6, Ki-67 and IL-21R and correlate with expanded T follicular helper (Tfh) cells or B cells that lack Bcl6, Ki-67 and IL-21R but express high levels of anti-apoptotic Bcl2 that negatively correlate with Tfh cells.
We observed an increase in hepatic macrophages during untreated SIV infection that was associated with a number of inflammatory and fibrosis mediators (TNFα, CCL3, TGFβ).
We observed that fCD8 cells, T follicular helper (Tfh) cells, and T follicular regulatory cells (Tfreg) were all elevated in chronic SIV infection. fCD8 cells of LVL animals tended to express more Gag-specific granzyme B and exhibited significantly greater killing than did HVL animals, and their cell frequencies were negatively correlated with viremia, suggesting a role in viremia control.
CH25H expression was interferon-dependent and induced by SIV infection in monkey-derived macrophages and PBMC cells, and 25-HC inhibited SIV infection both in permissive cell lines and primary monkey lymphocytes.
In addition, the increased occurrence of SIV infection accompanied by increases in the level of IL-10 in sera and lungs, in the spleen index and in the number of CD206-positive mouse alveolar macrophages but decreases in the level of TNF-α in sera and lungs, in the thymus index and in the number of CD80-positive mouse alveolar macrophages was observed in SIV-infected mice after low-level AFB1 exposure.
Here we show that chronic simian immunodeficiency virus (SIV) infection is characterized by an expansion of either lymph node germinal center (GC) B cells that co-express Bcl6, Ki-67 and IL-21R and correlate with expanded T follicular helper (Tfh) cells or B cells that lack Bcl6, Ki-67 and IL-21R but express high levels of anti-apoptotic Bcl2 that negatively correlate with Tfh cells.
Previously, we demonstrated that administration of a type I interferon receptor antagonist (IFN-1ant) during acute SIV infection of rhesus macaques results in increased virus replication and accelerated disease progression.
Our findings suggest that dysregulated miR-130a and miR-212 expression in colonic epithelium during chronic HIV/SIV infection can facilitate epithelial barrier disruption by downregulating OCLN and PPARγ expression.
Thus, our data show that blocking IFN-I signaling during chronic SIV infection suppresses IFN-I-related inflammatory pathways without increasing virus replication, and thus may constitute a safe therapeutic intervention in chronic HIV infection.
Simian immunodeficiency virus (SIV) infections further expand gut-homing adaptive NK cells but result in pathogenic suppression of CD3ζ-Zap70 signaling and function.
Thus, CXCR5+ CD8 T cells represent a unique subset of antiviral CD8 T cells that expand in LNs during chronic SIV infection and may play a significant role in the control of pathogenic SIV infection.
Dextran sulfate sodium (DSS-exposure) is an established animal model for experimental colitis that was recently shown to recapitulate the link between GI-tract damage and pathogenic features of SIV infection.
In this context, we paid a particular attention to B-cell-activating factor (BAFF), a key cytokine in B-cell development and immune response that is overproduced during HIV/SIV infection.
These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.
Dextran sulfate sodium (DSS-exposure) is an established animal model for experimental colitis that was recently shown to recapitulate the link between GI-tract damage and pathogenic features of SIV infection.
Th cells show an impaired response to chemotactic stimuli both in humans and in the pathogenic model of SIV infection, and this defect is due to hyperactivation of cofilin and inefficient actin polymerization.