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IFNalpha-blockade during ART-treated SIV infection lowers tissue vDNA, rescues immune function, and improves overall health

ABSTRACT: IFNalpha-blockade during ART-treated SIV infection lowers tissue vDNA, rescues immune function, and improves overall health

PROVIDER: PRJNA764769 | ENA |

REPOSITORIES: ENA

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IFNalpha-blockade during ART-treated SIV infection lowers tissue vDNA, rescues immune function, and improves overall health

Project description:The induction of type I interferons during acute viral infections drives local and systemic anti-viral responses. However, in chornic virus infection these type I interferon driven responses can be detrimental and can be characterized impaired immune responses (greater T cell exhaustion) and an overall decline in health outcomes. To parse out the role of type I IFN and assess the therapeutic impact of blocking type I IFN, we administered IFN-a blocking antibody to a cohort of SIV-infected ART treated Maccaca mulata. After 9 weeks of treatment (1 injection per week), we observed a significant reduction in the SIV-DNA levels in the lymphnode. This reduced SIV reservoir was seem with a systemic increase in immune cell subset signatures associated with better CD8 T cell function and lower plasma levels of TGF-beta. In addition, upon interruption of ART (16 weeks after ART initiation and after 16 rounds of anti-IFNa infusion), we observed that the non-human primates that underwent type I interferon blockade maintained better overall health and hemoglobin levels.

2021-09-27 | GSE184495 | GEO

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort3]

Project description:Unlike HIV infection, which progresses to AIDS absent suppressive anti-retroviral therapy (ART), nonpathogenic infections in natural hosts, such African green monkeys (AGMs), are characterized by a lack of gut microbial translocation and robust secondary lymphoid Natural Killer (NK) cell responses resulting in absence of chronic inflammation and limited SIV dissemination in lymph nodes (LN) B-cell-follicles, respectively. In a pathogenic infection model (i.e. ART-treated, SIVmac239-infected rhesus macaques; RMs), sequential Interleukin (IL)-21 and interferon (IFN)-alpha therapy generated terminally-differentiated blood NK cells (NKG2a/clowCD16+) with potent HLA-E-restricted activity in response to SIV-ENV peptides in contrast to control RMs, where less differentiated, IFN-gamma+ NK cells predominated. The frequency and cytolytic activity of NKG2a/clowCD16+ NK cells correlated with a reduction of replication-competent SIV in LN during ART and viral rebound delay following analytical treatment interruption. These data demonstrate that AGM-like NK cell differentiation profiles can be rescued in RMs to promote viral clearance in tissues.

2021-02-22 | GSE163442 | GEO

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort2]

2021-02-22 | GSE163441 | GEO

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort1]

2021-02-22 | GSE163440 | GEO

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques

Project description:IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques

| PRJNA686106 | ENA

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort1]

Project description:IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort1]

| PRJNA686107 | ENA

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort2]

Project description:IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort2]

| PRJNA686108 | ENA

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort3]

Project description:IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort3]

| PRJNA686109 | ENA

Peripheral Blood Biomarkers in ART-Suppressed, SIV-Infected Rhesus Macaques Predict Viral Rebound Following ART Discontinuation

Project description:The development of biomarkers that can predict viral rebound following discontinuation of antiretroviral therapy (ART) in HIV-1-infected humans would be an important advance in HIV-1 cure research. In a prior study, we initiated ART in 20 rhesus macaques on days 0, 1, 2, and 3 following SIVmac251 infection prior to plasma viremia1. Following 6 months of suppressive ART, we discontinued ART and observed viral rebound in 9 of 20 animals. Here we show that transcriptomic and proteomic signatures of inflammation and immune activation in peripheral blood during ART suppression predicted viral rebound following ART discontinuation. Higher levels of proinflammatory and cellular immune activation pathways, including TNF, IL-1, IL-6, monocyte, and T cell activation signaling pathways, correlated with viral rebound following ART discontinuation. Immune modulatory IL-10 and TGF-b signaling also correlated with viral rebound. We then validated these candidate biomarkers of viral rebound in a second cohort of SIV-infected, ART-suppressed macaques. Taken together, these data suggest that persistent upregulation of inflammatory and immune activation pathways despite suppressive ART may represent a peripheral blood biomarker signature of the rebound-competent viral reservoir. The development of interventions that target the viral reservoir and modulate this signature may open new avenues in HIV-1 cure research.

2023-08-30 | GSE203603 | GEO

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-02-22 | GSE163443 | GEO