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1.
Nutrients ; 13(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34684306

RESUMO

Selenium (Se) and zinc (Zn) are essential trace elements needed for appropriate immune system responses, cell signalling and anti-viral defence. A cross-sectional observational study was conducted at two hospitals in Ghent, Belgium, to investigate whether Se and/or Zn deficiency upon hospital admission correlates to disease severity and mortality risk in COVID-19 patients with or without co-morbidities. Trace element concentrations along with additional biomarkers were determined in serum or plasma and associated to disease severity and outcome. An insufficient Se and/or Zn status upon hospital admission was associated with a higher mortality rate and a more severe disease course in the entire study group, especially in the senior population. In comparison to healthy European adults, the patients displayed strongly depressed total Se (mean ± SD: 59.2 ± 20.6 vs. 84.4 ± 23.4 µg L-1) and SELENOP (mean ± SD: 2.2 ± 1.9 vs. 4.3 ± 1.0 mg L-1) concentrations at hospital admission. Particularly strong associations were observed for death risk of cancer, diabetes and chronic cardiac disease patients with low Se status, and of diabetes and obese patients with Zn deficiency. A composite biomarker based on serum or plasma Se, SELENOP and Zn at hospital admission proved to be a reliable tool to predict severe COVID-19 course and death, or mild disease course. We conclude that trace element assessment at hospital admission may contribute to a better stratification of patients with COVID-19 and other similar infectious diseases, support clinical care, therapeutic interventions and adjuvant supplementation needs, and may prove of particular relevance for patients with relevant comorbidities.

3.
J Infect Dis ; 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34417800

RESUMO

Clonal hematopoiesis, a common age-related phenomenon marked by expansion of cells with clonal hematopoiesis driver mutations, has been associated with all-cause mortality, cancer and cardiovascular disease. People with HIV (PWH) are at risk for non-AIDS related comorbidities such as atherosclerotic cardiovascular disease and cancer. In a cross-sectional cohort study, we compared clonal hematopoiesis prevalence in PWH on stable antiretroviral therapy, with prevalence in a cohort of overweight individuals and a cohort of age- and sex-matched population controls. The prevalence of clonal hematopoiesis adjusted for age was increased and clone size was larger in PWH compared to population controls. Clonal hematopoiesis is associated with low CD4 nadir, increased residual HIV-1 transcriptional activity and coagulation factors in PWH. Future studies on the effect of clonal hematopoiesis on the HIV reservoir, and non-AIDS related comorbidities are warranted.

4.
J Extracell Vesicles ; 10(10): e12122, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34429857

RESUMO

Separating extracellular vesicles (EV) from blood plasma is challenging and complicates their biological understanding and biomarker development. In this study, we fractionate blood plasma by combining size-exclusion chromatography (SEC) and OptiPrep density gradient centrifugation to study clinical context-dependent and time-dependent variations in the biomolecular landscape of systemically circulating EV. Using pooled blood plasma samples from breast cancer patients, we first demonstrate the technical repeatability of blood plasma fractionation. Using serial blood plasma samples from HIV and ovarian cancer patients (n = 10) we next show that EV carry a clinical context-dependent and/or time-dependent protein and small RNA composition, including miRNA and tRNA. In addition, differential analysis of blood plasma fractions provides a catalogue of putative proteins not associated with systemically circulating EV. In conclusion, the implementation of blood plasma fractionation allows to advance the biological understanding and biomarker development of systemically circulating EV.

5.
Nat Commun ; 12(1): 3727, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140517

RESUMO

Clonal expansion of HIV-infected cells contributes to the long-term persistence of the HIV reservoir in ART-suppressed individuals. However, the contribution from cell clones that harbor inducible proviruses to plasma viremia is poorly understood. Here, we describe a single-cell approach to simultaneously sequence the TCR, integration sites and proviral genomes from translation-competent reservoir cells, called STIP-Seq. By applying this approach to blood samples from eight participants, we show that the translation-competent reservoir mainly consists of proviruses with short deletions at the 5'-end of the genome, often involving the major splice donor site. TCR and integration site sequencing reveal that cell clones with predicted pathogen-specificity can harbor inducible proviruses integrated into cancer-related genes. Furthermore, we find several matches between proviruses retrieved with STIP-Seq and plasma viruses obtained during ART and upon treatment interruption, suggesting that STIP-Seq can capture clones that are responsible for low-level viremia or viral rebound.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , HIV-1/metabolismo , Provírus/genética , Análise de Célula Única/métodos , Viremia/virologia , Linfócitos T CD4-Positivos/virologia , DNA Viral/sangue , Infecções por HIV/virologia , HIV-1/genética , HIV-1/patogenicidade , Humanos , Ionomicina/farmacologia , Masculino , Pessoa de Meia-Idade , Filogenia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Deleção de Sequência , Carga Viral/genética
6.
Front Immunol ; 12: 661990, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953724

RESUMO

Long-term changes in the immune system of successfully treated people living with HIV (PLHIV) remain incompletely understood. In this study, we assessed 108 white blood cell (WBC) populations in a cohort of 211 PLHIV on stable antiretroviral therapy and in 56 HIV-uninfected controls using flow cytometry. We show that marked differences exist in T cell maturation and differentiation between PLHIV and HIV-uninfected controls: PLHIV had reduced percentages of CD4+ T cells and naïve T cells and increased percentages of CD8+ T cells, effector T cells, and T helper 17 (Th17) cells, together with increased Th17/regulatory T cell (Treg) ratios. PLHIV also exhibited altered B cell maturation with reduced percentages of memory B cells and increased numbers of plasmablasts. Determinants of the T and B cell composition in PLHIV included host factors (age, sex, and smoking), markers of the HIV reservoir, and CMV serostatus. Moreover, higher circulating Th17 percentages were associated with higher plasma concentrations of interleukin (IL) 6, soluble CD14, the gut homing chemokine CCL20, and intestinal fatty acid binding protein (IFABP). The changes in circulating lymphocytes translated into functional changes with reduced interferon (IFN)- γ responses of peripheral blood mononuclear cells to stimulation with Candida albicans and Mycobacterium tuberculosis. In conclusion, this comprehensive analysis confirms the importance of persistent abnormalities in the number and function of circulating immune cells in PLHIV on stable treatment.


Assuntos
Antirretrovirais/uso terapêutico , Translocação Bacteriana/imunologia , Células Sanguíneas/patologia , Citomegalovirus/imunologia , Reservatórios de Doenças/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Células Sanguíneas/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Feminino , HIV-1/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th17/imunologia , Células Th17/patologia
7.
AIDS ; 35(12): 2025-2033, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34033590

RESUMO

OBJECTIVE: To evaluate time trends in pregnancies and pregnancy outcomes among women with HIV in Europe. DESIGN: European multicentre prospective cohort study. METHODS: EuroSIDA has collected annual cross-sectional audits of pregnancies between 1996 and 2015. Pregnancy data were extracted and described. Odds of pregnancy were modelled, adjusting for potential confounders using logistic regression with generalized estimating equations. RESULTS: Of 5535 women aged 16 to <50 years, 4217 (76.2%) had pregnancy information available, and 912 (21.6%) reported 1315 pregnancies. The proportions with at least one pregnancy were 28.1% (321/1143) in East, 24.5% (146/596) in North, 19.8% (140/706) in West/Central, 19.3% (110/569) in Central East and 16.2% (195/1203) in South Europe. Overall 319 pregnancies (24.3%) occurred in 1996-2002, 576 (43.8%) in 2003-2009 and 420 (31.9%) in 2010-2015. After adjustment, the odds of pregnancy were lower in 1996-2002, in South, Central East and East compared to West/Central Europe, in older women, those with low CD4+ cell count or with prior AIDS, and higher in those with a previous pregnancy or who were hepatitis C virus positive.Outcomes were reported for 999 pregnancies in 1996-2014, with 690 live births (69.1%), seven stillbirths (0.7%), 103 spontaneous (10.3%) and 199 medical abortions (19.9%). CONCLUSIONS: Around 20% of women in EuroSIDA reported a pregnancy, with most pregnancies after 2002, when more effective antiretroviral therapy became available. Substantial differences were seen between European regions. Further surveillance of pregnancies and outcomes among women living with HIV is warranted to ensure equal access to care.


Assuntos
Aborto Induzido , Infecções por HIV , Idoso , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Gravidez , Prevalência , Estudos Prospectivos
9.
Methods ; 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33992770

RESUMO

The development of an HIV-1 cure is hampered by the existence of a persistent (latent) reservoir that contains a small proportion of replication-competent intact proviruses which refuels viral replication upon treatment discontinuation. Therefore, an accurate evaluation and quantification of these (intact) proviruses is essential to determine the efficacy of HIV-1 cure strategies which aim to eliminate this reservoir. Here, we present two triplex digital PCR assays which resulted from a combination of two existing methods, the IPDA (a 2-colour digital PCR based method) and Q4PCR assays (4 colour qPCR method), and tested the functionality on a three-colour digital PCR platform. In the present paper, we provide a step-by-step experimental protocol for these triplex digital PCR assays and validate their performance on a latently infected Jurkat cell-line model and HIV-1 patient samples. Our data demonstrates the potential and flexibility of increasing the number of subgenomic regions of HIV-1 within the IPDA to acquire sensitive detection of the HIV-1 reservoir while benefitting from the advantages of a dPCR setup.

10.
J Infect Dis ; 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33974707

RESUMO

BACKGROUND: Understanding the genetic interplay between human hosts and infectious pathogens is crucial for how we interpret virulence factors. Here, we tested for associations between HIV and host genetics, and interactive genetic effects on viral load (VL) in HIV+ ART-naive clinical trial participants. METHODS: HIV genomes were sequenced and the encoded amino acid (AA) variants were associated with VL, human single nucleotide polymorphisms (SNPs) and imputed HLA alleles, using generalized linear models with Bonferroni correction. RESULTS: Human (388,501 SNPs) and HIV (3,010 variants) genetic data was available for 2,122 persons. Four HIV variants were associated with VL (p-values<1.66×10 -5). Twelve HIV variants were associated with a range of 1-512 human SNPs (p-value<4.28×10 -11). We found 46 associations between HLA alleles and HIV variants (p-values<1.29×10 -7). We found HIV variants and immunotypes when analyzed separately, were associated with lower VL, whereas the opposite was true when analyzed in concert. Epitope binding prediction showed HLA alleles to be weaker binders of associated HIV AA variants relative to alternative variants on the same position. CONCLUSIONS: Our results show the importance of immunotype specificity on viral antigenic determinants, and the identified genetic interplay puts emphasis that viral and human genetics should be studied in the context of each other.

11.
Genome Biol ; 22(1): 97, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823910

RESUMO

The integration of a viral genome into the host genome has a major impact on the trajectory of the infected cell. Integration location and variation within the associated viral genome can influence both clonal expansion and persistence of infected cells. Methods based on short-read sequencing can identify viral insertion sites, but the sequence of the viral genomes within remains unobserved. We develop PCIP-seq, a method that leverages long reads to identify insertion sites and sequence their associated viral genome. We apply the technique to exogenous retroviruses HTLV-1, BLV, and HIV-1, endogenous retroviruses, and human papillomavirus.

12.
Infect Dis Ther ; 10(2): 775-788, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33686573

RESUMO

INTRODUCTION: We report the 48-week results of an ongoing study to assess the efficacy and safety of switching older people with HIV to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). METHODS: This was a 96-week, phase 3b, open-label, single-arm study (GS-US-380-4449; NCT03405935). Virologically suppressed individuals aged ≥ 65 years receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen were switched to B/F/TAF. Primary endpoint was the percentage of participants with HIV-1 RNA < 50 copies/ml at week 24. RESULTS: Eighty-six participants (median age 69 [range 65-80] years; 87% male; 95% white) were enrolled and treated in five European countries. Rates of virologic suppression were 97.7% at week 24 and 90.7% at week 48; none had HIV-1 RNA ≥ 50 copies/ml, and 100% had virologic suppression by missing = excluded analysis at both time points. No treatment-emergent resistance was observed. There were no grade 3-4 study drug-related adverse events (AEs) or study drug-related serious AEs or deaths. Three AEs led to premature discontinuation; one (moderate abdominal discomfort) was attributed to the study drug by the investigator. At week 48, median changes from baseline in weight and estimated glomerular filtration rate were + 0.1 kg (interquartile range [IQR] - 1.0, 2.3) and - 6.0 ml/min (IQR - 10.2, 0.0), respectively. There were no clinically relevant changes from baseline to week 48 in fasting lipid parameters. Treatment satisfaction improved, and health-related quality of life was maintained from baseline through week 48. Median adherence to the study drug was 98.6% (IQR 96.0, 100). CONCLUSIONS: Switching to B/F/TAF was effective and well tolerated through 48 weeks in virologically suppressed adults aged ≥ 65 years. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03405935.

13.
JCI Insight ; 6(7)2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33630761

RESUMO

Chronic inflammation and immune dysfunction play a key role in the development of non-AIDS-related comorbidities. The aim of our study was to characterize the functional phenotype of immune cells in people living with HIV (PLHIV). We enrolled a cross-sectional cohort study of PLHIV on stable antiretroviral therapy and healthy controls. We assessed ex vivo cytokine production capacity and transcriptomics of monocytes and T cells upon bacterial, fungal, and viral stimulation. PLHIV exhibited an exacerbated proinflammatory profile in monocyte-derived cytokines, but not in lymphocyte-derived cytokines. Particularly, the production of the IL-1ß to imiquimod, E. coli LPS, and Mycobacterium tuberculosis was increased, and this production correlated with plasma concentrations of high-sensitivity C-reactive protein and soluble CD14. This increase in monocyte responsiveness remained stable over time in subsequent blood sampling after more than 1 year. Transcriptome analyses confirmed priming of the monocyte IL-1ß pathway, consistent with a monocyte-trained immunity phenotype. Increased plasma concentrations of ß-glucan, a well-known inducer of trained immunity, were associated with increased innate cytokine responses. Monocytes of PLHIV exhibited a sustained proinflammatory immune phenotype with priming of the IL-1ß pathway. Training of the innate immune system in PLHIV likely plays a role in long-term HIV complications and provides a promising therapeutic target for inflammation-related comorbidities.

14.
J Virus Erad ; 7(1): 100029, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33598311

RESUMO

Objectives: We aimed to investigate the motives, barriers and experiences of HIV-STAR study participants. The HIV-STAR study was an analytical HIV treatment interruption trial (ATI) aiming to evaluate the origin of viral rebound, conducted in Ghent, Belgium. Methods: A mixed-method study was performed among 11 participants of the HIV-STAR study. Two self-administered questionnaires with 32 and 23 items, respectively, assessed motives, barriers and experiences of the research participants. In-depth interviews were conducted to further explore and understand topics that had emerged from these surveys. Results: Motives of ATI study participants were primarily related to the improvement of their own health perspectives and to their contribution to find an HIV cure. Barriers for ATI participation mostly related to practical issues, such as difficulty in planning study visits. Ten out of 11 participants reported a very high overall satisfaction and were willing to participate in another ATI. This satisfaction was predominantly linked to clear communication and guidance. Invasive sampling during the ATI was less of a burden than anticipated by participants. However, most participants underestimated the emotional impact of HIV treatment interruption, which was associated with feelings of uncertainty and loss of control. Risk of HIV transmission because of viral rebound was also mentioned as burdensome during this phase. Conclusions: Involvement in an ATI was positively evaluated by HIV-STAR participants. Contributing to HIV cure research outweighed the burden of study participation for most participants. The latter aspects were attenuated by mutual decision making and the experience of empathy from the research team. Still, issues regarding privacy and the psychosocial impact of treatment interruption, including sexuality and HIV transmissibility, should be addressed in a better way.

15.
Nucleic Acids Res ; 49(8): e43, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33511400

RESUMO

Characterization of the epigenetic status of individual cells remains a challenge. Current sequencing approaches have limited coverage, and it is difficult to assign an epigenetic status to the transcription state of individual gene alleles in the same cell. To address these limitations, a targeted microscopy-based epigenetic visualization assay (EVA) was developed for detection and quantification of epigenetic marks at genes of interest in single cells. The assay is based on an in situ biochemical reaction between an antibody-conjugated alkaline phosphatase bound to the epigenetic mark of interest, and a 5'-phosphorylated fluorophore-labeled DNA oligo tethered to a target gene by gene-specific oligonucleotides. When the epigenetic mark is present at the gene, phosphate group removal by the phosphatase protects the oligo from λ-exonuclease activity providing a quantitative fluorescent readout. We applied EVA to measure 5-methylcytosine (5mC) and H3K9Ac levels at different genes and the HIV-1 provirus in human cell lines. To link epigenetic marks to gene transcription, EVA was combined with RNA-FISH. Higher 5mC levels at the silenced compared to transcribed XIST gene alleles in female somatic cells validated this approach and demonstrated that EVA can be used to relate epigenetic marks to the transcription status of individual gene alleles.


Assuntos
5-Metilcitosina/metabolismo , Epigênese Genética , Histonas/metabolismo , Hibridização in Situ Fluorescente/métodos , Análise de Célula Única/métodos , Acetilação , Linhagem Celular , Metilação de DNA , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Epigenômica , Feminino , Regulação da Expressão Gênica/genética , Inativação Gênica , HIV-1/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Provírus/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
16.
J Med Virol ; 93(5): 2971-2978, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33506953

RESUMO

The aim of this study was to describe the clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) among people living with HIV (PLWH) in Belgium. We performed a retrospective multicenter cohort analysis of PLWH with either laboratory-confirmed, radiologically diagnosed, or clinically suspected COVID-19 between February 15, 2020 and May 31, 2020. The primary endpoint was outcome of COVID-19. Secondary endpoints included rate of hospitalization and length of hospital stay and rate of Intensive Care Unit (ICU) admission and mechanical ventilation. One hundred and one patients were included in this study. Patients were categorized as having either laboratory-confirmed (n = 65), radiologically-diagnosed (n = 3), or clinically suspected COVID-19 (n = 33). The median age was 51.3 years (interquartile range [IQR] 41.3-57.3) and 44% were female. Ninety-four percent of patients were virologically suppressed and 67% had a CD4+ cell count more than or equal to 500 cells/µl. Overall, 46% of patients required hospitalization and the median length of hospital stay was 6 days (IQR 3-15). Age more than or equal to 50 years, Black Sub-Saharan African patients, and being on an integrase strand transfer inhibitor-based regimen were associated with being hospitalized. ICU admission and mechanical ventilation was required for 15% and 10% of all patients respectively. Overall, 9% of patients died while 78 (77%) patients made a full recovery. HIV patients with COVID-19 experienced a high degree of hospitalization despite having elevated CD4+ cell counts and a high rate of virologic suppression. Matched case-control studies are warranted to measure the impact that HIV may have on patients with COVID-19.


Assuntos
COVID-19/diagnóstico , COVID-19/epidemiologia , Infecções por HIV/epidemiologia , Adulto , Bélgica/epidemiologia , Contagem de Linfócito CD4 , COVID-19/terapia , Estudos de Casos e Controles , Feminino , Infecções por HIV/imunologia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Resultado do Tratamento
17.
iScience ; 24(1): 101881, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33364576

RESUMO

CD32 has raised conflicting results as a putative marker of the HIV-1 reservoir. We measured CD32 expression in tissues from viremic and virally suppressed humanized mice treated relatively early or late after HIV-1 infection with combined antiretroviral therapy. CD32 was expressed in a small fraction of the memory CD4+ T-cell subsets from different tissues in viremic and aviremic mice, regardless of treatment initiation time. CD32+ memory CD4+ T cells were enriched in cell-associated (CA) HIV-1 DNA but not in CA HIV-1 RNA as compared to the CD32-CD4+ fraction. Using multidimensional reduction analysis, several memory CD4+CD32+ T-cell clusters were identified expressing HLA-DR, TIGIT, or PD-1. Importantly, although tissue-resident CD32+CD4+ memory cells were enriched with translation-competent reservoirs, most of it was detected in memory CD32-CD4+ T cells. Our findings support that CD32 labels highly activated/exhausted memory CD4+ T-cell subsets that contain only a small proportion of the translation-competent reservoir.

18.
PLoS Pathog ; 16(10): e1009037, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33125439

RESUMO

Since SARS-CoV-2 appeared in the human population, the scientific community has scrambled to gather as much information as possible to find good strategies for the containment and treatment of this pandemic virus. Here, we performed a systematic review of the current (pre)published SARS-CoV-2 literature with a focus on the evidence concerning SARS-CoV-2 distribution in human tissues and viral shedding in body fluids. In addition, this evidence is aligned with published ACE2 entry-receptor (single cell) expression data across the human body to construct a viral distribution and ACE2 receptor body map. We highlight the broad organotropism of SARS-CoV-2, as many studies identified viral components (RNA, proteins) in multiple organs, including the pharynx, trachea, lungs, blood, heart, vessels, intestines, brain, male genitals and kidneys. This also implicates the presence of viral components in various body fluids such as mucus, saliva, urine, cerebrospinal fluid, semen and breast milk. The main SARS-CoV-2 entry receptor, ACE2, is expressed at different levels in multiple tissues throughout the human body, but its expression levels do not always correspond with SARS-CoV-2 detection, indicating that there is a complex interplay between virus and host. Together, these data shed new light on the current view of SARS-CoV-2 pathogenesis and lay the foundation for better diagnosis and treatment of COVID-19 patients.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pulmão/virologia , Pneumonia Viral/tratamento farmacológico , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/virologia , Feminino , Humanos , Pulmão/metabolismo , Masculino , Pandemias , Peptidil Dipeptidase A/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Receptores Virais/efeitos dos fármacos , Receptores Virais/metabolismo , SARS-CoV-2
19.
Int J Mol Sci ; 21(20)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086748

RESUMO

Interferons play a critical role in the innate immune response against a variety of pathogens, such as HIV-1. Recent studies have shown that long non-coding genes are part of a reciprocal feedforward/feedback relationship with interferon expression. They presumably contribute to the cell type specificity of the interferon response, such as the phenotypic and functional transition of macrophages throughout the immune response. However, no comprehensive understanding exists today about the IFN-lncRNA interplay in macrophages, also a sanctuary for latent HIV-1. Therefore, we completed a poly-A+ RNAseq analysis on monocyte-derived macrophages (MDMs) treated with members of all three types of IFNs (IFN-α, IFN-ε, IFN-γ or IFN-λ) and on macrophages infected with HIV-1, revealing an extensive non-coding IFN and/or HIV-1 response. Moreover, co-expression correlation with mRNAs was used to identify important (long) non-coding hub genes within IFN- or HIV-1-associated gene clusters. This study identified and prioritized IFN related hub lncRNAs for further functional validation.


Assuntos
HIV-1/fisiologia , Interferons/metabolismo , Macrófagos/metabolismo , Macrófagos/virologia , RNA Longo não Codificante/metabolismo , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma/genética
20.
Acta Clin Belg ; : 1-9, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32468932

RESUMO

OBJECTIVES: In the last decade, there has been increasing scientific and legislative focus on antiretroviral treatment (ART) for all people living with HIV. Especially early ART initiation, preferably during acute HIV infection, has been named as a promising strategy, both for the individual and for the society. This article will review the benefits and possible future applications of immediate ART initiation during acute HIV infection and explore the remaining hurdles towards this strategy. RESULTS: On an individual level, initiation of ART during acute HIV infection limits the viral reservoir, preserves immune function, and decreases systemic inflammation. In addition, obtaining viral suppression soon after infection can be beneficial for the society by decreasing the chance of onward HIV transmission. Reducing the transmission will reduce HIV incidence and can curtail HIV-related health expenditure. Furthermore, the favorable immunological and virological profile obtained by treating during acute HIV infection will form an ideal starting point for several HIV cure strategies. CONCLUSIONS: Initiation of ART during acute HIV infection has shown distinct benefits for the individual, for the society, and for future research on HIV cure. In order to implement this strategy, equal focus should be placed on early diagnosis.

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