scholarly journals Gut Microbiome Signatures Linked to HIV-1 Reservoir Size and Viremia Control

2021 ◽  
Author(s):  
Alessandra Borgognone ◽  
Marc Noguera-Julian ◽  
Bruna Oriol ◽  
Laura Noël-Romas ◽  
Marta Ruiz-Riol ◽  
...  
Keyword(s):  
Immune Activation ◽  
Gut Microbiome ◽  
Methanogenic Archaea ◽  
Longitudinal Assessment ◽  
Viral Control ◽  
Immune Mediated ◽  
Functional Profiling ◽  
Gene Richness ◽  
Study Intervention ◽  
Hiv 1

AbstractBackgroundThe potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial.ResultsViremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways, including methanogenesis and carbohydrate biosynthesis, were significantly decreased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size.ConclusionsThis proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption.

scholarly journals Host genetic associations with the gut microbiota in HIV-1-infected subjects: a pilot exploratory study

2018 ◽  
Author(s):  
Yolanda Guillén ◽  
Marc Noguera-Julian ◽  
Javier Rivera ◽  
Maria Casadellà ◽  
Muntsa Rocafort ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Methanogenic Archaea ◽  
Genetic Associations ◽  
Host Genetics ◽  
Genetic Landscape ◽  
Host Genetic ◽  
Gene Richness ◽  
The Impact ◽  
Hiv 1

AbstractThe impact of host genetics on gut microbial dynamics is debated. No study to date has investigated the possible role of host genetics in shaping the gut microbiota in HIV-1 infected subjects. With the aim of generating preliminary data to inform future host genetic studies, we performed an exploratory host exome analysis of 147 subjects either infected or at risk of becoming infected with HIV-1 from the MetaHIV cohort in Barcelona. Using a DNA microarray chip, we sought to identify host genetic variants associated to three specific microbial features with a potentially inheritable component, and which were previously found to be associated with gut dysbiosis in HIV infection, i.e.: gut enterotype, presence of methanogenic archaea and microbial gene richness. After correction for multiple comparisons, we did not observe any statistically significant association between the host’s genetic landscape and the explored gut microbiome traits. These findings will help design future, adequately-powered studies to assess the influence of host genetics in the microbiome of HIV-1-infected subjects.

scholarly journals Gag-Specific CD4+ T-Cell Frequency Is Inversely Correlated with Proviral Load and Directly Correlated with Immune Activation in Infection with Human Immunodeficiency Virus Type 2 (HIV-2) but Not HIV-1

2008 ◽  
Vol 82 (19) ◽  
pp. 9795-9799 ◽  
Author(s):  
Russell B. Foxall ◽  
Catarina S. Cortesão ◽  
Adriana S. Albuquerque ◽  
Rui S. Soares ◽  
Rui M. M. Victorino ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immune Activation ◽  
Proviral Load ◽  
Viral Control ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 2 (HIV-2) infection, unlike HIV-1 infection, is normally characterized by low rates of CD4 depletion and low-to-undetectable viremia. We found that the frequency of Gag-specific CD4+ T cells featured positive correlations with the expression of markers of CD4 activation and a negative correlation with peripheral blood mononuclear cell-associated proviral load in infection with HIV-2, in contrast with HIV-1. Moreover, HIV-2-infected individuals exhibited a greater ability to respond to HIV-1 Gag peptides (heterologous responses). Our data suggest a potential link between HIV-2-specific CD4 responses, immune activation, and viral control, which may in turn relate to the better prognosis associated with HIV-2 infection.

scholarly journals Alterations in the gut microbiome by HIV-1 infection or a high-fat diet associates with systemic immune activation and inflammation in double humanized-BLT mice

2020 ◽  
Author(s):  
Lance Daharsh ◽  
Amanda E. Ramer-Tait ◽  
Qingsheng Li
Keyword(s):  
Immune System ◽  
Systemic Inflammation ◽  
Immune Activation ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Human Immune System ◽  
Systemic Immune Activation ◽  
Human Immune ◽  
Hiv 1

AbstractBackgroundWhile the translatability of gut microbiome studies utilizing animal models to humans has proven difficult, studying the gut microbiome directly in humans is also challenging due to the existence of many confounding variables. Therefore, we utilized double humanized mice, which have both an engrafted stable human-like gut microbiome and functional human immune system. With this model, we were able to determine the in vivo impact of HIV-1 infection or a high-fat diet (HFD) on gut human microbiome composition, and its relationship with human immune cell activation and systemic inflammation.ResultsSurgery was performed on NSG mice to create humanized bone-marrow, liver, thymus mice (hu-mice). In order to create double hu-mice, the hu-mice were treated with broad spectrum antibiotics to deplete murine gut bacteria and subsequently transplanted with human fecal material from healthy human donors. We characterized 262 fecal samples from hu-mice, double hu-mice, and human fecal donors to determine the impact of HIV-1 infection or HFD on the gut microbiome and systemic immune activation and inflammation. We found that HIV-1 infection altered the human-like gut microbiome of double hu-mice, which was associated with decreased human CD4 T cells and increased systemic inflammation and immune activation. Further, using a HFD we induced gut microbial dysbiosis in double hu-mice which corresponded with increased systemic immune activation and inflammation.ConclusionsHere, we describe the changes in the human gut microbiome and human immune system due to HIV-1 infection or HFD using our double hu-mice model. HIV-1 infection led to changes in the composition of the human-like gut microbiome that was associated with human CD4 T cell loss and high levels of inflammation and immune activation. The HFD quickly changed the composition of the gut microbiome and led to systemic immune activation and inflammation. We further identified a subset of gut bacteria in HIV-1 infected and HFD fed double hu-mice that was closely associated with systemic inflammation and immune activation. This study demonstrated how double humanized mice can be used to study the complex in vivo interactions of the gut microbiome and human immune system in the context of both disease and diet.

scholarly journals ADAR1 Function Regulates Innate Immune Activation and Susceptibility to Viral Infections

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 34
Author(s):  
Maria Pujantell ◽  
Eva Riveira-Muñoz ◽  
Edurne García-Vidal ◽  
Lucía Gutiérrez-Chamorro ◽  
Roger Badia ◽  
...  
Keyword(s):  
Genetic Association ◽  
Immune Activation ◽  
Viral Infections ◽  
Association Studies ◽  
Innate Immune ◽  
Viral Control ◽  
Innate Immune Activation ◽  
Hiv 1

Viral infection induces innate intracellular antiviral defenses, aimed at restricting virus replication and spread. Therefore, understanding the role and function of innate immune modulators can help to establish novel strategies for viral control. Here, we explore the role of ADAR1 as a regulator of the HIV, HCV, and HPV infections, both in vitro and in vivo, in a genetic association study. Depletion of ADAR1 induced innate immune activation, observed by a significant increase in IFNB1 mRNA and CXCL10 expression. Further characterization of ADAR1 knockdown also showed upregulation of the RNA sensors MDA5 and RIG-I, increased IRF7 expression, and phosphorylation of STAT1. ADAR1 deficiency had differential effects depending on the virus tested: siADAR1 cells showed a significant reduction in HIV-1 infection, whereas ADAR1 knockdown suggested a proviral role in HCV and HPV infections. In addition, genetic association studies were performed in a cohort of 155 HCV/HIV individuals with chronic coinfection, and a cohort of 173 HPV/HIV-infected individuals was followed for a median of six years (range 0.1–24). Polymorphisms within the ADAR1 gene were found to be significantly associated with poor clinical outcome of HCV therapy and advanced liver fibrosis in a cohort of HCV/HIV-1-coinfected patients. Moreover, we identified the low-frequency haplotype AACCAT to be significantly associated with recurrent HPV dysplasia, suggesting a role for ADAR1 in the outcome of HPV infection in HIV+ individuals. In conclusion, we show that ADAR1 regulates innate immune activation and plays a key role in susceptibility to viral infections by either limiting or enhancing viral replication. Overall, ADAR1 could be a potential target for designing immune-modulating therapeutic strategies.

Methotrexate-Induced Shifts in the Human Gut Microbiome Decrease Immune Activation

2020 ◽  
Author(s):  
Renuka R. Nayak ◽  
Margaret Alexander ◽  
Ishani Deshpande ◽  
Kye Stapleton-Grey ◽  
Carles Ubeda ◽  
...  
Keyword(s):  
Immune Activation ◽  
Gut Microbiome ◽  
Human Gut ◽  
Human Gut Microbiome

scholarly journals Integrated analysis of lncRNA, miRNA and mRNA profiles reveals potential lncRNA functions during early HIV infection

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lianwei Ma ◽  
Hui Zhang ◽  
Yue Zhang ◽  
Hailong Li ◽  
Minghui An ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Immune Activation ◽  
Expression Profiles ◽  
Critical Role ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Target Mrnas ◽  
Immunodeficiency Virus ◽  
Mirna Sequencing ◽  
Hiv 1

Abstract Background Long noncoding RNAs (lncRNAs) can regulate gene expression in a cis-regulatory fashion or as “microRNA sponges”. However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear. Methods 3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNA cis-regulatory target mRNAs and constructing lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks. Results A total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate their cis-regulatory target mRNAs BTLA and ZAP70, respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulate HIF1A and TCF7L2, which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) with FOS, FOSB and JUN, which are associated with both immune activation and HIV-1 replication. Conclusions This study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.

scholarly journals Human Endogenous Retrovirus Expression Is Inversely Associated with Chronic Immune Activation in HIV-1 Infection

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e41021 ◽  
Author(s):  
Christopher E. Ormsby ◽  
Devi SenGupta ◽  
Ravi Tandon ◽  
Steven G. Deeks ◽  
Jeffrey N. Martin ◽  
...  
Keyword(s):  
Immune Activation ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Chronic Immune Activation ◽  
Hiv 1

scholarly journals Higher prevalence of viral control in HIV-1-infected women in serodiscordant relationships

PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0208401
Author(s):  
Kathryn Peebles ◽  
R. Scott McClelland ◽  
Julie Overbaugh ◽  
Barbra A. Richardson ◽  
Rose Bosire ◽  
...  
Keyword(s):  
Viral Control ◽  
Hiv 1
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