The Role of Inflammasome Activation in Early HIV Infection

Ekabe, Cyril Jabea; Clinton, Njinju Asaba; Kehbila, Jules; Franck, Ngangom Chouamo

doi:10.1155/2021/1487287

Cited by 16 publications

(11 citation statements)

References 43 publications

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“…Absent in melanoma 2 (AIM2) is a cytosolic sensor for double-stranded DNA (dsDNA) and tumor suppressor that is responsible for inflammasome activation and is involved in the host immune response to viruses and intracellular bacteria ( Saiga et al., 2012 ). AIM2 binds to HIV dsDNA and may trigger acute inflammation and pyroptosis ( Ekabe et al., 2021 ). Regarding the AIM2 rs2276405 polymorphism, to our knowledge, only one study showed a significant difference in the genotype frequencies of this Single Nucleotide Polymorphism (SNP) between individuals with and without TB in a Taiwanese population ( Liu et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

Sá

Souza

Neira-Goulart

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundTuberculosis (TB) and AIDS are the leading causes of infectious diseases death worldwide. Here, we investigated the relationship between from single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8, AIM2, CASP-1, IFI16, and IL-1β inflammasome genes, as well as the profiles of secreted proinflammatory cytokines (e.g., IL-1β, IL-18, IL-33, and IL-6) with the TB clinical profiles, TB-HIV coinfection, and IRIS onset.MethodsThe individuals were divided into four groups: TB-HIV group (n=88; 11 of them with IRIS), HIV-1 group (n=20), TB group (n=24) and healthy volunteers (HC) group (n=10), and were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. Real-time PCR was used to determine the genotypes of the Single Nucleotide Polymorphism (SNPs), and ELISA was used to measure the plasma cytokine levels. Unconditional logistic regression models were used to perform risk estimations.ResultsA higher risk for extrapulmonary TB was associated with the TT genotype (aOR=6.76; P=0.026) in the NLRP3 rs4612666 Single Nucleotide Polymorphism (SNP) and the C-C-T-G-C haplotype (aOR=4.99; P= 0.017) in the NLRP3 variants. This same Single Nucleotide Polymorphism (SNP) was associated with lower risk against extrapulmonary TB when the carrier allele C (aOR=0.15; P=0.021) was present. Among those with HIV-1 infections, a higher risk for TB onset was associated with the GA genotype (aOR=5.5; P=0.044) in the IL1-β rs1143634 Single Nucleotide Polymorphism (SNP). In contrast, lower risk against TB onset was associated with the A-G haplotype (aOR=0.17; P= 0.026) in the CARD8 variants. Higher IL-6 and IL-33 levels were observed in individuals with TB. A higher risk for IRIS onset was associated with CD8 counts ≤ 500 cells/mm3 (aOR=12.32; P=0.010), the presence of extrapulmonary TB (aOR=6.6; P=0.038), and the CT genotype (aOR=61.06; P=0.026) or carrier allele T (aOR=61.06; P=0.026) in the AIM2 rs2276405 Single Nucleotide Polymorphism (SNP), whereas lower risk against IRIS onset was associated with the AT genotype (aOR=0.02; P=0.033) or carrier allele T (aOR=0.02; P=0.029) in the CARD8 rs2043211 Single Nucleotide Polymorphism (SNP) and the T-G haplotype (aOR=0.07; P= 0.033) in the CARD8 variants. No other significant associations were observed.ConclusionsOur results depict the involvement of genetic polymorphisms of crucial innate immunity genes and proinflammatory cytokines in the clinical outcomes related to TB-HIV coinfection.

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Section: Discussionmentioning

confidence: 99%

Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

Sá

Souza

Neira-Goulart

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Except for IL-1α, rate of biomarker decay appeared unaffected by time since EDDI at enrollment, and those who started treatment immediately had faster declines in only 3 other markers. Although we did not directly evaluate inflammasomes in this study, our findings hint at a complex regulation of acute inflammation that depended on time since HIV infection and exogenous exposures [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use

Gilada¹,

Schnittman

White

et al. 2022

Open Forum Infectious Diseases

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Background Primary HIV is characterized by dynamic changes in viral load and innate and adaptive immune responses; it is unclear the extent to which time from acquisition to ART initiation and substance use impact these immunologic changes. Methods We studied plasma immune activation biomarkers, viral load, and CD4 + and CD8 + cell counts in participants from the Sabes primary infection study in Peru, who had been randomized to begin ART immediately after diagnosis vs. 24 weeks later. We modeled influence of substance use and duration of HIV infection on biomarkers at baseline and over 24 weeks. Results Compared to participants enrolled >30 days after HIV acquisition, participants enrolled during acute infection (<30 days) had higher mean IFN-γ and IFN-α2a (1.7-fold and 3.8-fold IQR higher, respectively). Participants enrolled >30 days after HIV acquisition had higher mean baseline CD8 + cell count (2.7 times the IQR). Alcohol use (positive PEth level) was associated with elevated IFN-γ, TNF-α, and IL-12p70, and smoking with higher MIP-1α, TNF-α, and IL-12p70. Most biomarkers declined more quickly in participants who initiated ART immediately, however substance use and duration of HIV infection at enrollment had little influence on rate of decline. Conclusion IFN-γ and other biomarkers are elevated during early primary infection, when exposure to HIV antigens is high. Immune activation decreased most quickly in those who started ART during acute/early primary infection. Higher CD8 + cell counts and a trend toward higher sCD163 levels during the 30 days after acquisition suggest the onset of compensatory responses and immune exhaustion.

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“…Intracellular PRRs that detect viral nucleic acids include the cytosolic DNA sensor cyclic guanosine adenosine synthase (cGAS) [106][107][108][109] and interferon-inducible protein 16 (IFI16) [110], and the cytosolic RNA sensors retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), melanoma differentiation-associated protein 5 (MDA5) [111], and laboratory of genetics and physiology 2 (LGP2) [112]. Other PPRs that sense nucleic acids include a subset of Toll-like receptors (TLR-3, -7, -8, -9 and -13), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) [25,[113][114][115][116]. Furthermore, nucleic acids have been suggested to activate the NLRP1 inflammasome, cytokine expression and the pyroptosis of CD4+ T cells [25,[116][117][118][119].…”

Section: Hiv-1 Rnas Inducing Inflammatory Signalsmentioning

confidence: 99%

Chronic HIV Transcription, Translation, and Persistent Inflammation

Kilroy,

Leal,

Henderson

2024

Viruses

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People with HIV exhibit persistent inflammation that correlates with HIV-associated comorbidities including accelerated aging, increased risk of cardiovascular disease, and neuroinflammation. Mechanisms that perpetuate chronic inflammation in people with HIV undergoing antiretroviral treatments are poorly understood. One hypothesis is that the persistent low-level expression of HIV proviruses, including RNAs generated from defective proviral genomes, drives the immune dysfunction that is responsible for chronic HIV pathogenesis. We explore factors during HIV infection that contribute to the generation of a pool of defective proviruses as well as how HIV-1 mRNA and proteins alter immune function in people living with HIV.

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The Role of Inflammasome Activation in Early HIV Infection

Cited by 16 publications

References 43 publications

Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use

Chronic HIV Transcription, Translation, and Persistent Inflammation

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