Increased Prevalence of Unstable HLA-C Variants in HIV-1 Rapid-Progressor Patients

Stefani, Chiara; Sangalli, Antonella; Locatelli, Elena; Federico, Tania; Malerba, Giovanni; Silva, Bosco Christiano Maciel da; Silva, Alberto Jose Duarte Da; Casseb, Jorge; Argañaraz, Enrique R.; Ruggiero, Alessandra; Zipeto, Donato

doi:10.3390/ijms232314852

Cited by 2 publications

(2 citation statements)

References 35 publications

(42 reference statements)

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“…We found that the HIV-infected individuals had an inverse association between HIV-1 viral load and CD4 + T cell count. Further, the progressors had a significantly higher VL and reduced CD4 count as compared to the LTNPs, as also previously reported [99][100][101]. Association studies have further shown that type-1 IFNs-IFN-α and IFN-β, were inversely correlated with viral load and positively correlated with CD4 count.…”

Section: Discussionsupporting

confidence: 83%

MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors

Pawar,

Gokavi,

Wakhare

et al. 2023

Viruses

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HIV infection impairs host immunity, leading to progressive disease. An anti-retroviral treatment efficiently controls viremia but cannot completely restore the immune dysfunction in HIV-infected individuals. Both host and viral factors determine the rate of disease progression. Among the host factors, innate immunity plays a critical role; however, the mechanism(s) associated with dysfunctional innate responses are poorly understood among HIV disease progressors, which was investigated here. The gene expression profiles of TLRs and innate cytokines in HIV-infected (LTNPs and progressors) and HIV-uninfected individuals were examined. Since the progressors showed a dysregulated TLR-mediated innate response, we investigated the role of TLR agonists in restoring the innate functions of the progressors. The stimulation of PBMCs with TLR3 agonist-poly:(I:C), TLR7 agonist-GS-9620 and TLR9 agonist-ODN 2216 resulted in an increased expression of IFN-α, IFN-β and IL-6. Interestingly, the expression of IFITM3, BST-2, IFITM-3, IFI-16 was also increased upon stimulation with TLR3 and TLR7 agonists, respectively. To further understand the molecular mechanism involved, the role of miR-155 was explored. Increased miR-155 expression was noted among the progressors. MiR-155 inhibition upregulated the expression of TLR3, NF-κB, IRF-3, TNF-α and the APOBEC-3G, IFITM-3, IFI-16 and BST-2 genes in the PBMCs of the progressors. To conclude, miR-155 negatively regulates TLR-mediated cytokines as wel l as the expression of host restriction factors, which play an important role in mounting anti-HIV responses; hence, targeting miR-155 might be helpful in devising strategic approaches towards alleviating HIV disease progression.

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Section: Discussionsupporting

confidence: 83%

MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors

Pawar,

Gokavi,

Wakhare

et al. 2023

Viruses

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“…The results showed a significant correlation between rapid progression to AIDS and the presence of two or one unstable HLA-C variants. Thus, unstable HLA-C variants both at genotype and at allele levels and rapid progression to Aids [71].…”

Section: Discussionmentioning

confidence: 99%

People Living with HIV (PLWH) Controllers Induce High Production of IFN-γ to Gag Epitope

Da Silva,

Hildebrando

et al. 2023

Preprint

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We report the characterization of phenotype, genotype, and functional parameters such as CD4+ T cell, viral load, HIV-1 genotype, class I HLA genotype, CCR5 polymorphism, and IFN-γ producing cells from a cohort of 37 people living with HIV-1 (PLWH) (viremic controllers, were compared those on antiretroviral therapy (ART) from two sites in São Paulo, Brazil. Half the PLWH (51.4%) were classified as viremic controllers (Controller group - CG), compared to 48.6% were on ART. As expected, controllers showed baseline higher levels of CD4+ T cells and nadir compared to those under ART, confirming the ability of HIV-1 controllers to preserve these cells even in the absence of ART. IFN-γ-producing cells showed greater magnitude to the HIV peptides Gag in controllers (p<0.03). Our results demonstrated that HLA protective alleles are associated with strong production of IFN-γ to Gag, Nef and RT epitopes in people living with HIV controllers.

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Increased Prevalence of Unstable HLA-C Variants in HIV-1 Rapid-Progressor Patients

Cited by 2 publications

References 35 publications

MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors

MiR-155 Negatively Regulates Anti-Viral Innate Responses among HIV-Infected Progressors

People Living with HIV (PLWH) Controllers Induce High Production of IFN-γ to Gag Epitope

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