HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) hijack the host exosomal machinery as an additional mechanism of infection and evasion of the immune system, modifying the small RNA (smRnA) cargo during infection. We characterized the surface epitopes of extracellular vesicles (eVs) from plasma HIV/HCV-coinfected patients and their smRNA cargo profile, by comparing different isolation procedures. Six EVs isolation procedures were compared: ultracentrifugation, and five different polyethylene glycol-based methods (commercial, combined with a column purification step and two custom); and two RNA commercial kits (phenol and non-phenol based) were used. Highthroughput sequencing of smRNAs was performed. Exosomal surface epitopes were analyzed by the MACSPlex Exosome Kit. Four miRNAs displayed differences among protocols (hsa-miR-205-5p and hsa-let-7a/b/f-5p). The selection of RNA isolation kit impacted on the detection of miRNAs and other smRNAs, where the phenol-based RNA isolation kit performed acceptably. EVs surface was enriched with HLA-DR/DP/DQ, CD81, and CD8. There were three liver-specific miRNAs overexpressed (let-7a-5p, miR-21-5p and hsa-miR-122-5p), thus, EVs cargo might reflect liver disease evolution. Other smRNAs such as piwi-interacting RNAs were also detected for the first time. Custom polyethylene glycol precipitation-based methods combined with an RNA phenol-based kit yielded the higher number of smRnAs for eVs isolated from plasma HiV/HcV patients.

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“…patients characteristics. Samples were recruited under the COVIHEP group as previously described 30 .…”

Section: Methodsmentioning

confidence: 99%

Comparison of methods and characterization of small RNAs from plasma extracellular vesicles of HIV/HCV coinfected patients

Martínez-González

Brochado-Kith

Gómez-Sanz

et al. 2020

Sci Rep

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“…Although the combined antiretroviral therapy (ART) can successfully suppress HIV viremia and delays the progression of disease [ 1 ], the chronic infection requires lifetime treatment due to the viral persistence in latent reservoirs [ 2 , 3 , 4 ]. Importantly, a significant percentage of HIV-infected individuals has hepatitis C virus (HCV) co-infection [ 5 ] resulting in increased HIV reservoir size [ 6 ]. The advent of ART has improved survival of HIV-infected adults and children leading to chronic illnesses such as different pulmonary diseases [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

et al. 2020

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Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are involved in chronic pulmonary diseases occurring at high frequency among HIV-infected individuals. Immunoglobulin superantigens bind to the variable regions of either the heavy or light chain of immunoglobulins (Igs). Glycoprotein 120 (gp120) of HIV-1 is a typical immunoglobulin superantigen interacting with the heavy chain, variable 3 (VH3) region of human Igs. The present study investigated whether immunoglobulin superantigen gp120 caused the release of different classes of proinflammatory and immunoregulatory mediators from HLMCs. The results show that gp120 from different clades induced the rapid (30 min) release of preformed mediators (histamine and tryptase) from HLMCs. gp120 also caused the de novo synthesis of cysteinyl leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) from HLMCs. Incubation (6 h) of HLMC with gp120 induced the release of angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The activating property of gp120 was mediated through the interaction with IgE VH3+ bound to FcεRI. Our data indicate that HIV gp120 is a viral superantigen, which induces the release of different proinflammatory, angiogenic, and lymphangiogenic factors from HLMCs. These observations could contribute to understanding, at least in part, the pathophysiology of chronic pulmonary diseases in HIV-infected individuals.

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“…Fifty milliliters of blood samples were taken from all study patients. Briefly, fresh PBMCs were obtained and rCD4+ T cells were purified by negative selection with EasySep™ Human Resting CD4+ T-Cell Isolation Kit (Stemcell Technologies, Vancouver, Canada), as described previously by our group [ 9 ]. The purity of CD4+CD25-CD69-HLA/DR-T cells was assessed by flow cytometry as >99%.…”

Section: Methodsmentioning

confidence: 99%

“…Values of 2-LTR circle DNA molecules in rCD4 T+ cells and rCD4 T- PBMCs were subtracted from the integrated HIV-DNA value. Information regarding the methodology and procedures involved in the assessment of proviral DNA has been previously described by our group elsewhere [ 9 ].…”

Section: Methodsmentioning

confidence: 99%

“…Spontaneous HCV clearance occurs in 10–15% of acute infections in HCV-monoinfected individuals but only in less than 10% of HIV-1 infected patients [ 8 ]. Our group recently determined that HIV/HCV coinfection enhances the size of HIV proviral DNA in patients exposed to HCV contrasting to HIV monoinfected subjects, in both HCV spontaneous viral clarifiers (HIV+/HCV−) and HCV chronically infected individuals (HIV+/HCV+) [ 9 ]. However, it is unknown whether coinfection also affects proviral transcription and if this could significantly affect the strategies for the elimination of HIV-1 reservoir in these subjects.…”

Section: Introductionmentioning

confidence: 99%

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Hepatitis C Virus Influences HIV-1 Viral Splicing in Coinfected Patients

Martínez-Román

López-Huertas

Crespo-Bermejo

et al. 2020

JCM

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Coinfection with hepatitis C virus (HCV) influences HIV reservoir size. However, it is unknown whether this coinfection also induces a higher provirus transcription. Viral transcription is promoted by synergy between cellular factors such as NF-κB and the viral regulator Tat. The impact of HCV coinfection on HIV provirus transcription was analyzed in resting (r)CD4 T+ cells (CD3+CD4+CD25-CD69-HLADR-) and rCD4 T cells-depleted PBMCs (rCD4 T- PBMCs) from a multicenter cross-sectional study of 115 cART-treated HIV patients: 42 HIV+/HCV+ coinfected individuals (HIV+/HCV+), 34 HIV+ patients with HCV spontaneous clearance (HIV+/HCV−) and 39 HIV patients (HIV+). Viral transcription was assessed in total RNA through the quantification of unspliced, single spliced, and multiple spliced viral mRNAs by qPCR. Linear correlations between viral reservoir size and viral splicing were determined. A 3-fold increase of multiple spliced transcripts in rCD4 T+ cells of HIV+/HCV+ patients was found compared to HIV+ individuals (p < 0.05). As Tat is synthesized by multiple splicing, the levels of Tat were also quantified in these patients. Significant differences in single and multiple spliced transcripts were also observed in rCD4 T- PBMCs. Levels of multiple spliced mRNAs were increased in rCD4 T+ cells isolated from HIV+/HCV+ subjects, which could indicate a higher Tat activity in these cells despite their resting state.

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HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study

Cited by 23 publications

References 49 publications

Comparison of methods and characterization of small RNAs from plasma extracellular vesicles of HIV/HCV coinfected patients

Comparison of methods and characterization of small RNAs from plasma extracellular vesicles of HIV/HCV coinfected patients

HIV gp120 Induces the Release of Proinflammatory, Angiogenic, and Lymphangiogenic Factors from Human Lung Mast Cells

Hepatitis C Virus Influences HIV-1 Viral Splicing in Coinfected Patients

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