ABSTRACT: Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection
Project description:A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Our study evaluates the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. Microarrays were used to characterize changes in gene expression in the tongue mucosa that occur during chronic SIV infection. Dorsal tongue tissues from healthy uninfected macaques and macaques with chronic stage SIV infection were used for RNA extraction and hybridization on Affymetrix microarrays.
Project description:A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Our study evaluates the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. Microarrays were used to characterize changes in gene expression in the dorsal tongue epithelium that occur during chronic SIV infection. Epithelial cells were laser microdissected from dorsal tongue tissue sections from healthy uninfected macaques and macaques with chronic stage SIV infection and used for RNA extraction and hybridization on Affymetrix microarrays.
Project description:The objectives of this study were to determine the molecular mechanisms of host response during transition from primary to chronic SIV infection in the oral mucosa of rhesus macaques Transcriptioinal profiles were determined for 2 rhesus macaques infected for 6 wk with SIVmac251 and compared to profiles of 3 uninfected healthy controls
Project description:The objectives of this study were to determine the molecular mechanisms of host response during transition from primary to chronic SIV infection in the oral mucosa of rhesus macaques
2009-01-13 | GSE14351 | GEO
Project description:Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection
Project description:A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Our study evaluates the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. Microarrays were used to characterize changes in gene expression in the tongue mucosa that occur during chronic SIV infection.
Project description:A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Our study evaluates the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. Microarrays were used to characterize changes in gene expression in the dorsal tongue epithelium that occur during chronic SIV infection.
Project description:Natural SIV infection of sooty mangabeys (SMs) does not progress to disease despite chronic virus replication. In contrast to pathogenic SIV infection of rhesus macaques (RMs), chronic SIV infection of SMs is characterized by low immune activation. To elucidate the mechanisms underlying this phenotype, we longitudinally assessed host gene expression in SIV-infected SMs and RMs. We found that acute SIV infection of SMs is consistently associated with a robust innate immune response, including widespread up-regulation of interferon-stimulated genes (ISGs). Our findings indicate that active immune regulatory mechanisms, rather than intrinsically attenuated innate immune responses, underlie the low immuneactivation of chronically SIV-infected SMs. We infected 5 SMs with SIVsmm and assessed their gene expression in RNA derived from whole blood at 3,7,10,14,30 and 180 days post-infection using Rhesus Affymetrix GeneChips. As a comparison, we also analyzed gene expression in 4 RMs infected with SIVsmm, and 8 RMs infected with SIVmac239, a classical pathogenic SIV.
Project description:HIV/SIV associated oral mucosal disease/dysfunction (HAOMD) (gingivitis/periodontitis/salivary adenitis) represents a major comorbidity affecting HIV patients on anti-retroviral therapy. Using a systems biology approach, we investigated molecular changes (mRNA/microRNA) underlying HAOMD and its modulation by phytocannabinoids [delta-9-tetrahydrocannabinol (Δ9-THC)] in uninfected (n=5) and SIV-infected rhesus macaques untreated (VEH-untreated/SIV; n=7) or treated with vehicle (VEH/SIV; n=3) or Δ9-THC (THC/SIV; n=3). Relative to controls fewer mRNAs were upregulated in THC/SIV compared to VEH-untreated/SIV macaques. Gene enrichment analysis showed differential enrichment of biological functions involved in anti-viral defense, Type-I interferon, Toll-like receptor, RIG-1 and IL1R signaling in VEH-untreated/SIV macaques. We focused on the anti-ER-stress anterior gradient-2 (AGR2), epithelial barrier protecting and anti-dysbiotic WAP Four-Disulfide Core Domain 2 (WFDC2), and glucocorticoid-induced anti-inflammatory TSC22D3 (TSC22-domain family member 3) that were significantly downregulated in OPM of VEH-untreated/SIV macaques. All three proteins localized to minor salivary gland acini and secretory ducts and showed enhanced and reduced expression in OPM of THC/SIV and VEH/SIV macaques, respectively. Additionally, inflammation associated miR-21, miR-142-3p and miR-29b showed significantly higher expression in OPM of VEH-untreated/SIV macaques. TSC22D3 was validated as a target of miR-29b. These preliminary translational findings suggest that phytocannabinoids may safely and effectively reduce oral inflammatory responses in HIV/SIV and other diseases.
Project description:Natural SIV infection of sooty mangabeys (SMs) does not progress to disease despite chronic virus replication. In contrast to pathogenic SIV infection of rhesus macaques (RMs), chronic SIV infection of SMs is characterized by low immune activation. To elucidate the mechanisms underlying this phenotype, we longitudinally assessed host gene expression in SIV-infected SMs and RMs. We found that acute SIV infection of SMs is consistently associated with a robust innate immune response, including widespread up-regulation of interferon-stimulated genes (ISGs). Our findings indicate that active immune regulatory mechanisms, rather than intrinsically attenuated innate immune responses, underlie the low immuneactivation of chronically SIV-infected SMs.