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1.
J Med Virol ; 93(11): 6116-6123, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34375002

RESUMO

Virus invasion activates the host's innate immune response, inducing the production of numerous cytokines and interferons to eliminate pathogens. Except for viral DNA/RNA, viral proteins are also targets of pattern recognition receptors. Membrane-bound receptors such as Toll-like receptor (TLR)1, TLR2, TLR4, TLR6, and TLR10 relate to the recognition of viral proteins. Distinct TLRs perform both protective and detrimental roles for a specific virus. Here, we review viral proteins serving as pathogen-associated molecular patterns and their corresponding TLRs. These viruses are all enveloped, including respiratory syncytial virus, hepatitis C virus, measles virus, herpesvirus human immunodeficiency virus, and coronavirus, and can encode proteins to activate innate immunity in a TLR-dependent way. The TLR-viral protein relationship plays an important role in innate immunity activation. A detailed understanding of their pathways contributes to a novel direction for vaccine development.


Assuntos
Imunidade Inata , Padrões Moleculares Associados a Patógenos/metabolismo , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo , Proteínas Virais/metabolismo , Viroses/imunologia , Vírus/imunologia , Animais , HIV/imunologia , HIV/metabolismo , HIV/patogenicidade , Hepacivirus/imunologia , Hepacivirus/metabolismo , Hepacivirus/patogenicidade , Herpesviridae/imunologia , Herpesviridae/metabolismo , Herpesviridae/patogenicidade , Humanos , Vírus do Sarampo/imunologia , Vírus do Sarampo/metabolismo , Vírus do Sarampo/patogenicidade , Padrões Moleculares Associados a Patógenos/química , Vírus Sinciciais Respiratórios/imunologia , Vírus Sinciciais Respiratórios/metabolismo , Vírus Sinciciais Respiratórios/patogenicidade , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Proteínas Virais/química , Viroses/virologia , Vírus/metabolismo , Vírus/patogenicidade
2.
BMC Infect Dis ; 21(1): 561, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118891

RESUMO

BACKGROUND: People living with human immunodeficiency virus (HIV) with immuno-virological discordant responses are at an increased risk to develop acquired immunodeficiency syndrome (AIDS) and severe non AIDS events which are risk factors for death. This study was aimed to assess prevalence of immuno- virological discordant responses and associated risk factors among highly active antiretroviral therapy (HAART) users in Tigray, Northern Ethiopia. METHODS: A cross sectional study was conducted from September to December 30, 2016 on 260 people living with HIV who started first line HAART from January 2008 to March 2016 at Mekelle hospital and Ayder comprehensive specialized hospital. Baseline and follow-up clinical data and CD4+ result were collected from patient charts. Besides, socio-demographic data and blood samples for CD4 + count and viral load measurement were collected during data collection period. Fisher's exact test, bivariate and multivariate logistic regressions were used for data analysis. P-value < 0.05 with 95% CI was considered as statistically significant. RESULT: Among the 260 study participants, 8.80% (95% Confidence Interval (CI) =8.77-8.84%) and 2.70% (95% CI = 2.68-2.72%) had virological and immunological discordant responses, respectively with an overall immuno-virological discordance response of 11.50% (95% CI = 11.46-11.54%). The median age of the study participants at HAART initiation was 35 (IQR: 28-44 years). More than half (58.1%) of the study participants were females. Age at or below 35 years old at HAART initiation (AOR ((95% CI) = 4.25(1.48-12.23), p = 0.007)), male gender ((Adjusted Odds Ratio (AOR) (95% CI) =1.71(1.13-1.10), p = 0.029)), type of regimen given ((AOR(95% CI) = 0.30 (0.10-0.88), p = 0.028)) and good treatment adherence ((AOR (95% CI) = 0.12 (0.030-0.0.48), p = 0.003)) were associated risk factors for virological discordant response. Likewise, immunological discordant response was associated with tuberculosis co-infections (p = 0.016), hepatitis B virus co-infections (p = 0.05) and low CD4+ count (≤100 cells/µl) at baseline (p = 0.026). CONCLUSIONS: Over all, immuno-virological discordance response was 11.5% in the study area. Males, low baseline CD4+ count, poor/fair treatment adherence, and TB and HBV co-infections were significantly associated with higher immuno-virological discordance. We recommend that decision of patient treatment outcome, regimen change and patient management response should be done using trends of both viral load and CD4+ count concurrently.


Assuntos
Antirretrovirais , Infecções por HIV , HIV , Adulto , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos Transversais , Etiópia/epidemiologia , Feminino , HIV/efeitos dos fármacos , HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Resultado do Tratamento , Carga Viral
3.
Front Immunol ; 12: 688747, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122453

RESUMO

Despite the ability of combination antiretroviral therapy (cART) to increase the life expectancy of patients infected with human immunodeficiency virus (HIV), viral reservoirs persist during life-long treatment. Notably, two cases of functional cure for HIV have been reported and are known as the "Berlin Patient" and the "London Patient". Both patients received allogeneic hematopoietic stem cell transplantation from donors with homozygous CCR5 delta32 mutation for an associated hematological malignancy. Therefore, there is growing interest in creating an HIV-resistant immune system through the use of gene-modified autologous hematopoietic stem cells with non-functional CCR5. Moreover, studies in CXCR4-targeted gene therapy for HIV have also shown great promise. Developing a cure for HIV infection remains a high priority. In this review, we discuss the increasing progress of coreceptor-based hematopoietic stem cell gene therapy, cART, milder conditioning regimens, and shock and kill strategies that have important implications for designing potential strategies aiming to achieve a functional cure for the majority of people with HIV.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Genética , Infecções por HIV/terapia , HIV/imunologia , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/cirurgia , Leucemia Mieloide Aguda/cirurgia , Animais , Fármacos Anti-HIV/efeitos adversos , Seleção do Doador , Terapia Genética/efeitos adversos , Alemanha , HIV/patogenicidade , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/genética , Doença de Hodgkin/imunologia , Doença de Hodgkin/virologia , Homozigoto , Interações Hospedeiro-Patógeno , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/virologia , Doadores Vivos , Londres , Mutação , Receptores CCR5/genética , Transplante Homólogo , Resultado do Tratamento
5.
BMC Infect Dis ; 21(1): 466, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022850

RESUMO

BACKGROUND: Pulmonary tuberculosis (TB) in people living with HIV (PLH) frequently presents as sputum smear-negative. However, clinical trials of TB in adults often use smear-positive individuals to ensure measurable bacterial responses following initiation of treatment, thereby excluding HIV-infected patients from trials. METHODS: In this prospective case cohort study, 118 HIV-seropositive TB patients were assessed prior to initiation of standard four-drug TB therapy and at several time points through 35 days. Sputum bacillary load, as a marker of treatment response, was determined serially by: smear microscopy, Xpert MTB/RIF, liquid culture, and colony counts on agar medium. RESULTS: By all four measures, patients who were baseline smear-positive had higher bacterial loads than those presenting as smear-negative, until day 35. However, most smear-negative PLH had significant bacillary load at enrolment and their mycobacteria were cleared more rapidly than smear-positive patients. Smear-negative patients' decline in bacillary load, determined by colony counts, was linear to day 7 suggesting measurable bactericidal activity. Moreover, the decrease in bacterial counts was comparable to smear-positive individuals. Increasing cycle threshold values (Ct) on the Xpert assay in smear-positive patients to day 14 implied decreasing bacterial load. CONCLUSION: Our data suggest that smear-negative PLH can be included in clinical trials of novel treatment regimens as they contain sufficient viable bacteria, but allowances for late exclusions would have to be made in sample size estimations. We also show that increases in Ct in smear-positive patients to day 14 reflect treatment responses and the Xpert MTB/RIF assay could be used as biomarker for early treatment response.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Antituberculosos/uso terapêutico , Carga Bacteriana/efeitos dos fármacos , Soropositividade para HIV , HIV/imunologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Testes Diagnósticos de Rotina , Feminino , Seguimentos , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/virologia , Humanos , Masculino , Microscopia , Técnicas de Amplificação de Ácido Nucleico , Estudos Prospectivos , Resultado do Tratamento , Tuberculose Pulmonar/virologia
6.
Viruses ; 13(4)2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33916360

RESUMO

My memories of Steve go back over 50 years. While precise dates are no longer in my memory bank, circumstances and emotions remain alive and easy to recall. These memories tell the story of a remarkable human being, a true practitioner of his craft always, faithful to the basic principles of scientific pursuit, with integrity, honesty, and enthusiasm well beyond the norm. We had a professional symbiotic relationship that lasted over 20 years, resulting in over 50 publications in scientific journals and meeting abstracts. During that time, our fortunes rose in tandem, and when it was time to go our separate ways, he was more than ready to flourish on his own. Our personal friendship remained constant, and we enjoyed sharing meals and stories with family and friends over the years. In retrospect, I take pride in having played a role in a portion of his remarkable scientific journey. A few key anecdotes will illustrate some aspects of this summary. By way of a disclaimer, this is not a comprehensive review of the vast field of viral oncology and the selection of references is intentionally narrow. No slight is intended to the many outstanding investigators that were our contemporaries and at times collaborators during the period from the early 70s to the mid-80s.


Assuntos
HIV/imunologia , Narração , Retroviridae , História do Século XX , História do Século XXI , Humanos , Masculino , Pesquisa/educação , Pesquisa/história
7.
Front Immunol ; 12: 657679, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815419

RESUMO

Human Immunodeficiency Virus (HIV) and Simian Immunodeficiency Virus (SIV) are associated with severe perturbations in the gut mucosal environment characterized by massive viral replication and depletion of CD4 T cells leading to dysbiosis, breakdown of the epithelial barrier, microbial translocation, immune activation and disease progression. Multiple mechanisms play a role in maintaining homeostasis in the gut mucosa and protecting the integrity of the epithelial barrier. Among these are the secretory IgA (sIgA) that are produced daily in vast quantities throughout the mucosa and play a pivotal role in preventing commensal microbes from breaching the epithelial barrier. These microbe specific, high affinity IgA are produced by IgA+ plasma cells that are present within the Peyer's Patches, mesenteric lymph nodes and the isolated lymphoid follicles that are prevalent in the lamina propria of the gastrointestinal tract (GIT). Differentiation, maturation and class switching to IgA producing plasma cells requires help from T follicular helper (Tfh) cells that are present within these lymphoid tissues. HIV replication and CD4 T cell depletion is accompanied by severe dysregulation of Tfh cell responses that compromises the generation of mucosal IgA that in turn alters barrier integrity leading to commensal bacteria readily breaching the epithelial barrier and causing mucosal pathology. Here we review the effect of HIV infection on Tfh cells and mucosal IgA responses in the GIT and the consequences these have for gut dysbiosis and mucosal immunopathogenesis.


Assuntos
Microbioma Gastrointestinal/imunologia , Infecções por HIV/imunologia , HIV/imunologia , Homeostase/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunoglobulina A/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Comunicação Celular/imunologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Humanos , Imunidade nas Mucosas , Imunoglobulina A Secretora/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Plasmócitos/imunologia , Plasmócitos/metabolismo , Transdução de Sinais , Vírus da Imunodeficiência Símia/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo
8.
PLoS Pathog ; 17(4): e1009522, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33872331

RESUMO

Although HIV infection inhibits interferon responses in its target cells in vitro, interferon signatures can be detected in vivo soon after sexual transmission, mainly attributed to plasmacytoid dendritic cells (pDCs). In this study, we examined the physiological contributions of pDCs to early HIV acquisition using coculture models of pDCs with myeloid DCs, macrophages and the resting central, transitional and effector memory CD4 T cell subsets. pDCs impacted infection in a cell-specific manner. In myeloid cells, HIV infection was decreased via antiviral effects, cell maturation and downregulation of CCR5 expression. In contrast, in resting memory CD4 T cells, pDCs induced a subset-specific increase in intracellular HIV p24 protein expression without any activation or increase in CCR5 expression, as measured by flow cytometry. This increase was due to reactivation rather than enhanced viral spread, as blocking HIV entry via CCR5 did not alter the increased intracellular p24 expression. Furthermore, the load and proportion of cells expressing HIV DNA were restricted in the presence of pDCs while reverse transcriptase and p24 ELISA assays showed no increase in particle associated reverse transcriptase or extracellular p24 production. In addition, pDCs also markedly induced the expression of CD69 on infected CD4 T cells and other markers of CD4 T cell tissue retention. These phenotypic changes showed marked parallels with resident memory CD4 T cells isolated from anogenital tissue using enzymatic digestion. Production of IFNα by pDCs was the main driving factor for all these results. Thus, pDCs may reduce HIV spread during initial mucosal acquisition by inhibiting replication in myeloid cells while reactivating latent virus in resting memory CD4 T cells and retaining them for immune clearance.


Assuntos
Células Dendríticas/virologia , Infecções por HIV/virologia , HIV/imunologia , Interferon-alfa/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Células Dendríticas/imunologia , Citometria de Fluxo , HIV/genética , HIV/fisiologia , Proteína do Núcleo p24 do HIV/genética , Proteína do Núcleo p24 do HIV/metabolismo , Infecções por HIV/imunologia , Humanos , Células Mieloides/imunologia , Células Mieloides/virologia , Fenótipo
9.
Clin Immunol ; 227: 108727, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33887436

RESUMO

With the global spread of coronavirus disease 2019 (COVID-19), the important role of natural killer (NK) cells in the control of various viral infections attracted more interest, via non-specific activation, such as antibody-dependent cell-mediated cytotoxicity (ADCC) and activating receptors, as well as specific activation, such as memory-like NK generation. In response to different viral infections, NK cells fight viruses in different ways, and different NK subsets proliferate. For instance, cytomegalovirus (CMV) induces NKG2C + CD57 + KIR+ NK cells to expand 3-6 months after hematopoietic stem cell transplantation (HSCT), but human immunodeficiency virus (HIV) induces KIR3DS1+/KIR3DL1 NK cells to expand in the acute phase of infection. However, the similarities and differences among these processes and their molecular mechanisms have not been fully discussed. In this article, we provide a summary and comparison of antiviral mechanisms, unique subset expansion and time periods in peripheral blood and tissues under different conditions of CMV, HIV, Epstein-Barr virus (EBV), COVID-19 and hepatitis B virus (HBV) infections. Accordingly, we also discuss current clinical NK-associated antiviral applications, including cell therapy and NK-related biological agents, and we state the progress and future prospects of NK cell antiviral treatment.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Interações entre Hospedeiro e Microrganismos/imunologia , Células Matadoras Naturais/imunologia , Citotoxicidade Celular Dependente de Anticorpos , COVID-19/sangue , Citomegalovirus/imunologia , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , Hepatite B/sangue , Hepatite B/imunologia , Hepatite B/virologia , Vírus da Hepatite B/imunologia , Herpesvirus Humano 4/imunologia , Humanos , SARS-CoV-2/imunologia , Receptores Toll-Like/metabolismo
10.
Medicine (Baltimore) ; 100(17): e25510, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907100

RESUMO

ABSTRACT: While pediatric human immunodeficiency virus (HIV) testing has been more focused on children below 18 months through prevention of mother to child transmission of HIV (PMTCT), the yield of this approach remains unclear comparatively to testing children above 18 months through routine provider-initiated testing and counselling (PITC). This study aimed at assessing and comparing the HIV case detection and antiretroviral therapy (ART) enrolment among children below and above 18 months of age in Cameroon. This information is required to guide the investments in HIV testing among children and adolescents.We conducted a cross-sectional study where we invited parents visiting or receiving HIV care in 3 hospitals to have their children tested for HIV. HIV testing was done using polymerase chain reaction (PCR) and antibody rapid tests for children <18 months and those ≥18 months, respectively. We compared HIV case detection and ART initiation between the 2 subgroups of children and this using Chi-square test at 5% significant level.A total of 4079 children aged 6 weeks to 15 years were included in the analysis. Compared with children <18 months, children group ≥18 months was 4-fold higher among those who enrolled in the study (80.3% vs 19.7%, P < .001); 3.5-fold higher among those who tested for HIV (77.6% vs 22.4%, P < .001); 6-fold higher among those who tested HIV+ (85.7% vs 14.3%, P = .24), and 11-fold higher among those who enrolled on ART (91.7% vs 8.3%, P = .02).Our results show that 4 out of 5 children who tested HIV+ and over 90% of ART enrolled cases were children ≥18 months. Thus, while rolling out PCR HIV testing technology for neonates and infants, committing adequate and proportionate resources in antibody rapid testing for older children is a sine quo none condition to achieve an acquired immunodeficiency syndrome (AIDS)-free generation.


Assuntos
Sorodiagnóstico da AIDS/estatística & dados numéricos , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Programas de Rastreamento/estatística & dados numéricos , Adolescente , Fatores Etários , Camarões/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , HIV/imunologia , Infecções por HIV/epidemiologia , Humanos , Lactente , Masculino , Programas de Rastreamento/métodos
11.
Medicine (Baltimore) ; 100(17): e25632, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907119

RESUMO

ABSTRACT: The 17 Provincial Institutes of Health and Environment (PIHEs) in Korea use HIV antibody, antigen, and Western blot assays for confirmatory testing of HIV infection. The Korea Disease Control and Prevention Agency (KDCA) has further included p24 antigen neutralization and nucleic acid tests (NATs) since 2015. Our study aimed to investigate the effect of this new testing algorithm on the confirmation rate of HIV infection.Annual changes, from 2012 through 2017, in positive or indeterminate HIV confirmatory results were compared for the two algorithms between the PIHEs and the KDCA. Fiebig stages and Western blot p31 band were used to identify the diagnostic proportions of acute or early chronic HIV for the two algorithms.The number of positive cases in the samples requested from PIHEs for reconfirmation by the KDCA has steadily increased from 10.3% in 2014 to 33.3% in 2017. However, the number of indeterminate cases dropped sharply, from 71.9% in 2014 to 14.0% in 2017. The results for the p31 reactive band were 27.4% and 88.4% for the KDCA and PIHEs, respectively. Of positive cases reported by the KDCA, 22.9% were in the early acute stage and Fiebig stages I to II.The new testing algorithm has improved the diagnosis of HIV infections in the early acute stage. Early confirmatory diagnosis can prevent secondary transmission of HIV and provide early treatment opportunities for people living with HIV infection.


Assuntos
Algoritmos , Western Blotting/estatística & dados numéricos , Infecções por HIV/diagnóstico , Imunoensaio/estatística & dados numéricos , Técnicas de Amplificação de Ácido Nucleico/estatística & dados numéricos , Diagnóstico Precoce , HIV/imunologia , Anticorpos Anti-HIV/análise , Antígenos HIV/análise , Infecções por HIV/epidemiologia , Humanos , República da Coreia/epidemiologia , Sensibilidade e Especificidade
12.
Medicine (Baltimore) ; 100(17): e25678, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907138

RESUMO

ABSTRACT: HIV infection has become a chronic disease, with a lower mortality, but a consequent increase in age-related noninfectious comorbidities. Metabolic disorders have been linked to the effect of cART as well to the effects of immune activation and chronic inflammation. Whereas it is known that aging is intrinsically associated with hyperinflammation and immune system deterioration, the relative impact of chronic HIV infection on such inflammatory and immune activation has not yet been studied focusing on an elderly HIV-infected population.The objectives of the study were to assess 29 blood markers of immune activation and inflammation using an ultrasensitive technique, in HIV-infected patients aged ≥75 years with no or 1 comorbidity (among hypertension, renal disease, neoplasia, diabetes mellitus, cardiovascular disease, stroke, dyslipidemia, and osteoporosis), in comparison with age-adjusted HIV-uninfected individuals to identify whether biomarkers were associated with comorbidities. Wilcoxon nonparametric tests were used to compare the levels of each marker between control and HIV groups; logistic regression to identify biomarkers associated to comorbidity in the HIV group and principal component analysis (PCA) to determine clusters associated with a group or a specific comorbidity.A total of 111 HIV-infected subjects were included from the Dat'AIDS cohort and compared to 63 HIV-uninfected controls. In the HIV-infected group, 4 biomarkers were associated with the risk of developing a comorbidity: monocyte chemoattractant protein-1 (MCP-1), neurofilament light chain (NF-L), neopterin, and soluble CD14. Six biomarkers (interleukin [IL]-1B, IL-7, IL-18, neopterin, sCD14, and fatty acid-binding protein) were significantly higher in the HIV-infected group compared to the control group, 11 biomarkers (myeloperoxydase, interleukin-1 receptor antagonist, tumor necrosis factor receptor 1, interferon-gamma, MCP-1, tumor necrosis factor receptor 2, IL-22, ultra sensitivity C-reactive protein, fibrinogen, IL-6, and NF-L) were lower. Despite those differences, PCA to determine clusters associated with a group or a specific comorbidity did not reveal clustering nor between healthy control and HIV-infected patients neither between the presence of comorbidity within HIV-infected group.In this highly selected geriatric HIV population, HIV infection does not seem to have an additional impact on age-related inflammation and immune disorder. Close monitoring could have led to optimize prevention and treatment of comorbidities, and have limited both immune activation and inflammation in the aging HIV population.


Assuntos
Envelhecimento/imunologia , Infecções por HIV/sangue , Infecções por HIV/imunologia , HIV/imunologia , Mediadores da Inflamação/imunologia , Idoso , Envelhecimento/sangue , Biomarcadores/sangue , Doença Crônica , Estudos de Coortes , Comorbidade , Feminino , França , Avaliação Geriátrica , Humanos , Imunidade Ativa , Inflamação , Mediadores da Inflamação/sangue , Modelos Logísticos , Masculino , Análise de Componente Principal , Estatísticas não Paramétricas
13.
Front Immunol ; 12: 609884, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679745

RESUMO

Predictive models are becoming more and more commonplace as tools for candidate antigen discovery to meet the challenges of enabling epitope mapping of cohorts with diverse HLA properties. Here we build on the concept of using two key parameters, diversity metric of the HLA profile of individuals within a population and consideration of sequence diversity in the context of an individual's CD8 T-cell immune repertoire to assess the HIV proteome for defined regions of immunogenicity. Using this approach, analysis of HLA adaptation and functional immunogenicity data enabled the identification of regions within the proteome that offer significant conservation, HLA recognition within a population, low prevalence of HLA adaptation and demonstrated immunogenicity. We believe this unique and novel approach to vaccine design as a supplement to vitro functional assays, offers a bespoke pipeline for expedited and rational CD8 T-cell vaccine design for HIV and potentially other pathogens with the potential for both global and local coverage.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV/imunologia , Interações Hospedeiro-Patógeno/imunologia , Aprendizado de Máquina , Antígenos Virais/genética , Antígenos Virais/imunologia , Epitopos de Linfócito T/imunologia , Variação Genética , Genoma Viral , Antígenos HLA/imunologia , Humanos , Peptídeos/imunologia , Proteoma , Proteínas Virais
14.
J Immunol Methods ; 493: 113019, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33705735

RESUMO

BACKGROUND: The determination of IgG levels and their subclasses can provide clinically relevant information on the status of the immune system. Here we determined the sensitivity and reproducibility of the quantification of IgG subclasses from Dried Blood Spots (DBS) in Malawian uninfected infants exposed to HIV (HEU). METHODS: Sixty paired samples of serum and DBS from HEU infants were used. Samples were collected from 1, 6, and 24-month old infants. IgGs concentrations from both serum and DBS were analyzed by BN ProSpec Siemens assay, using a different setting for sample dilutions. The reproducibility of the DBS method was tested on 10 samples run twice, starting from the DBS extraction process. To assess the systematic, proportional, and random differences, we computed the Passing-Bablok regression, and the Bland-Altman analysis to estimate the total mean bias between the two tests. RESULTS: The IgG isotypes concentrations from serum and DBS showed significant differences in all the comparisons. Generally, the DBS method underestimated IgG subclasses' values showing a recovery range between 51.2% and 77.6%. Passing Bablok regression on age-based groups showed agreement for IgG, IgG1, and IgG2, but not for IgG3 and IgG4. The mean bias obtained with the Bland Altman test varied largely depending on IgG isotypes (-0.02-2.21 g/l) Coefficient of variation <7.0% was found in the repeated tests for IgG, IgG1, IgG3, and IgG4, while it was 12.4% for IgG2. CONCLUSIONS: Varying degrees of differences were seen in the IgGs measurement in the two different matrices. In IgGs analysis, the DBS method offers promise for population-based research, but the results should be carefully evaluated and considered as a relative value since they are not equivalent to the serum concentrations.


Assuntos
Teste em Amostras de Sangue Seco , HIV/imunologia , Isotipos de Imunoglobulinas/sangue , Feminino , Humanos , Isotipos de Imunoglobulinas/imunologia , Lactente , Gravidez , Reprodutibilidade dos Testes
15.
Front Immunol ; 12: 634386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777022

RESUMO

Neutrophils are important components of the innate immune system that mediate pathogen defense by multiple processes including phagocytosis, release of proteolytic enzymes, production of reactive oxygen species, and neutrophil extracellular trap formation. Abnormalities of neutrophil count and function have been described in the setting of HIV infection, with the majority of antiretroviral agents (ARVs), excluding zidovudine, having been reported to correct neutropenia. Questions still remain, however, about their impact on neutrophil function, particularly the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment. In this context, the effects of protease inhibitors and integrase strand transfer inhibitors, in particular, on neutrophil function remain poorly understood and deserve further study. Besides mediating hemostatic functions, platelets are increasingly recognized as critical role players in the immune response against infection. In the setting of HIV, these cells have been found to harbor the virus, even in the presence of antiretroviral therapy (ART) potentially promoting viral dissemination. While HIV-infected individuals often present with thrombocytopenia, they have also been reported to have increased platelet activation, as measured by an upregulation of expression of CD62P (P-selectin), CD40 ligand, glycoprotein IV, and RANTES. Despite ART-mediated viral suppression, HIV-infected individuals reportedly have sustained platelet activation and dysfunction. This, in turn, contributes to persistent immune activation and an inflammatory vascular environment, seemingly involving neutrophil-platelet-endothelium interactions that increase the risk for development of comorbidities such as cardiovascular disease (CVD) that has become the leading cause of morbidity and mortality in HIV-infected individuals on treatment, clearly underscoring the importance of unraveling the possible etiologic roles of ARVs. In this context, abacavir and ritonavir-boosted lopinavir and darunavir have all been linked to an increased risk of CVD. This narrative review is therefore focused primarily on the role of neutrophils and platelets in HIV transmission and disease, as well as on the effect of HIV and the most common ARVs on the numbers and functions of these cells, including neutrophil-platelet-endothelial interactions.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Plaquetas/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , HIV/patogenicidade , Neutrófilos/efeitos dos fármacos , Animais , Plaquetas/imunologia , Plaquetas/metabolismo , Plaquetas/virologia , HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno , Humanos , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/virologia , Ativação Plaquetária/efeitos dos fármacos , Resultado do Tratamento
16.
Rev Med Virol ; 31(6): e2228, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33694220

RESUMO

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We performed a systematic review to examine whether prior clinical studies that compared the effects of CQ and HCQ to a control for the treatment of non-SARS-CoV2 infection supported the use of these agents in the present SARS-CoV2 outbreak. PubMed, EMBASE, Scopus and Web of Science (PROSPERO CRD42020183429) were searched from inception through 2 April 2020 without language restrictions. Of 1766 retrieved reports, 18 studies met our inclusion criteria, including 17 prospective controlled studies and one retrospective study. CQ or HCQ were compared to control for the treatment of infectious mononucleosis (EBV, n = 4), warts (human papillomavirus, n = 2), chronic HIV infection (n = 6), acute chikungunya infection (n = 1), acute dengue virus infection (n = 2), chronic HCV (n = 2), and as preventive measures for influenza infection (n = 1). Survival was not evaluated in any study. For HIV, the virus that was most investigated, while two early studies suggested HCQ reduced viral levels, four subsequent ones did not, and in two of these CQ or HCQ increased viral levels and reduced CD4 counts. Overall, three studies concluded CQ or HCQ were effective; four concluded further research was needed to assess the treatments' effectiveness; and 11 concluded that treatment was ineffective or potentially harmful. Prior controlled clinical trials with CQ and HCQ for non-SARS-CoV2 viral infections do not support these agents' use for the SARS-CoV2 outbreak.


Assuntos
Febre de Chikungunya/tratamento farmacológico , Cloroquina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Mononucleose Infecciosa/tratamento farmacológico , Dengue Grave/tratamento farmacológico , Verrugas/tratamento farmacológico , Alphapapillomavirus/efeitos dos fármacos , Alphapapillomavirus/imunologia , Alphapapillomavirus/patogenicidade , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/virologia , Febre de Chikungunya/imunologia , Febre de Chikungunya/patologia , Febre de Chikungunya/virologia , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/imunologia , Vírus Chikungunya/patogenicidade , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/imunologia , Vírus da Dengue/patogenicidade , HIV/efeitos dos fármacos , HIV/imunologia , HIV/patogenicidade , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/imunologia , Hepacivirus/patogenicidade , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Humanos , Mononucleose Infecciosa/imunologia , Mononucleose Infecciosa/patologia , Mononucleose Infecciosa/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Dengue Grave/imunologia , Dengue Grave/patologia , Dengue Grave/virologia , Resultado do Tratamento , Verrugas/imunologia , Verrugas/patologia , Verrugas/virologia
18.
J Immunoassay Immunochem ; 42(4): 444-452, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-33750262

RESUMO

Hepatitis B virus (HBV) is a leading cause of liver pathology, which has remained a serious public health challenge in spite of the availability of hepatitis B vaccine discovered about 40 years ago. People living with human immunodeficiency virus (PLHIV) are more at risk of hepatic problems as liver complications appear and progresses faster, owing to their immunocompromised status. This study seeks to determine HBV exposure, serological pattern, and HBV susceptibility among PLHIV. One hundred and fifty PLHIV were enrolled for the study. About 5 mL of blood was collected, processed, and tested for markers of hepatitis B virus: HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc. Twenty-eight (18.7%) had at least one serological marker while 122 (81.3%) tested negative to all the markers. The prevalence of HBsAg in this study was 8.7%, anti-HBs prevalence was 10%, while HBeAg was 2.7%, anti-HBe 6.0%, and anti-HBc 6.7%. Higher HBsAg, HBeAg, and anti-HBc prevalence were observed among the male participants with 13.9%, 5.6%, and 13.9%, respectively, while the female participants had more anti-HBs and anti-HBe of 1.8% and 6.1%, respectively. Age group 51-60 years had the highest prevalence of HBsAg (17.7%), HBeAg (11.8%), and anti-HBe (11.8%) while age group 31-40 years had the highest prevalence of anti-HBs (14.8%) and anti-HBe (9.8%). This study revealed the different serologic patterns of HBV infection among PLHIV and that susceptibility to HBV infection among PLHIV is high.


Assuntos
Infecções por HIV/imunologia , HIV/imunologia , Vírus da Hepatite B/imunologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/sangue , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Adulto Jovem
19.
Front Immunol ; 12: 614276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717099

RESUMO

The human immune system relies on the capability of CD8+ T cells to patrol body cells, spot infected cells and eliminate them. This cytotoxic response is supposed to be limited to infected cells to avoid killing of healthy cells. To enable this, CD8+ T cells have T Cell Receptors (TCRs) which should discriminate between self and non-self through the recognition of antigenic peptides bound to Human Leukocyte Antigen class I (HLA-I) complexes-i.e., HLA-I immunopeptidomes-of patrolled cells. The majority of these antigenic peptides are produced by proteasomes through either peptide hydrolysis or peptide splicing. Proteasome-generated cis-spliced peptides derive from a given antigen, are immunogenic and frequently presented by HLA-I complexes. Theoretically, they also have a very large sequence variability, which might impinge upon our model of self/non-self discrimination and central and peripheral CD8+ T cell tolerance. Indeed, a large variety of cis-spliced epitopes might enlarge the pool of viral-human zwitter epitopes, i.e., peptides that may be generated with the exact same sequence from both self (human) and non-self (viral) antigens. Antigenic viral-human zwitter peptides may be recognized by CD8+ thymocytes and T cells, induce clonal deletion or other tolerance processes, thereby restraining CD8+ T cell response against viruses. To test this hypothesis, we computed in silico the theoretical frequency of zwitter non-spliced and cis-spliced epitope candidates derived from human proteome (self) and from the proteomes of a large pool of viruses (non-self). We considered their binding affinity to the representative HLA-A*02:01 complex, self-antigen expression in Medullary Thymic Epithelial cells (mTECs) and the relative frequency of non-spliced and cis-spliced peptides in HLA-I immunopeptidomes. Based on the present knowledge of proteasome-catalyzed peptide splicing and neglecting CD8+ TCR degeneracy, our study suggests that, despite their frequency, the portion of the cis-spliced peptides we investigated could only marginally impinge upon the variety of functional CD8+ cytotoxic T cells (CTLs) involved in anti-viral response.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Tolerância Imunológica , Peptídeos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Processamento de Proteína , Sequência de Aminoácidos , Apresentação do Antígeno/imunologia , Deleção Clonal/imunologia , Epitopos de Linfócito T/imunologia , HIV/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Modelos Moleculares , Peptídeos/imunologia , Ligação Proteica/imunologia , Conformação Proteica , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Transcriptoma
20.
J Am Heart Assoc ; 10(7): e019709, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33749311

RESUMO

Background We aimed to investigate whether there are differences in cardiac structure and systolic and diastolic function evaluated by 2-dimensional echocardiography among men living with versus without HIV in the era of combination antiretroviral therapy. Methods and Results We performed a cross-sectional analysis of 1195 men from MACS (Multicenter AIDS Cohort Study) who completed a transthoracic echocardiogram examination between 2017 and 2019. Associations between HIV serostatus and echocardiographic indices were assessed by multivariable regression analyses, adjusting for demographics and cardiovascular risk factors. Among men who are HIV+, associations between HIV disease severity markers and echocardiographic parameters were also investigated. Average age was 57.1±11.9 years; 29% of the participants were Black, and 55% were HIV+. Most men who were HIV+ (77%) were virally suppressed; 92% received combination antiretroviral therapy. Prevalent left ventricular (LV) systolic dysfunction (ejection fraction <50%) was low and HIV serostatus was not associated with left ventricular ejection fraction. Multivariable adjustment models showed that men who were HIV+ versus those who were HIV- had greater LV mass index and larger left atrial diameter and right ventricular (RV) end-diastolic area; lower RV function; and higher prevalence of diastolic dysfunction. Higher current CD4+ T cell count ≥400 cell/mm3 versus <400 was associated with smaller LV diastolic volume and RV area. Virally suppressed men who were HIV+ versus those who were HIV- had higher indexed LV mass and left atrial areas and greater diastolic dysfunction. Conclusions HIV seropositivity was independently associated with greater LV mass index, left atrial and RV sizes, lower RV function and diastolic abnormalities, but not left ventricular ejection fraction, which may herald a future predisposition to heart failure with preserved ejection fraction among men living with HIV.


Assuntos
Ecocardiografia/métodos , Anticorpos Anti-HIV/imunologia , HIV/imunologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/fisiopatologia , Idoso , Estudos Transversais , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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