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The intestinal microbiota is an "invisible organ" in the human body, with diverse components and complex interactions. Homeostasis of the intestinal microbiota plays a pivotal role in maintaining the normal physiological process and regulating immune homeostasis. By reviewing more than one hundred related studies concerning HIV infection and intestinal microbiota from 2011 to 2023, we found that human immunodeficiency virus (HIV) infection can induce intestinal microbiota dysbiosis, which not only worsens clinical symptoms but also promotes the occurrence of post-sequelae symptoms and comorbidities. In the early stage of HIV infection, the intestinal mucosal barrier is damaged and a persistent inflammatory response is induced. Mucosal barrier damage and immune injury play a pivotal role in promoting the post-sequelae symptoms caused by HIV infection. This review summarizes the relationship between dysbiosis of the intestinal microbiota and mucosal barrier damage during HIV infection and discusses the potential mechanisms of intestinal barrier damage induced by intestinal microbiota dysbiosis and inflammation. Exploring these molecular mechanisms might provide new ideas to improve the efficacy of HIV treatment and reduce the incidence of post-sequelae symptoms.
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Background: Microbial translocation (MT) is a characteristic of human immunodeficiency virus (HIV) infection. Whether MT is also a biomarker of different immune responses to antiretroviral therapy (ART) received by people living with HIV (PLWH) is not known. Methods: We examined the presence of MT in a cohort of 33 HIV-infected immunological responders (IRs) and 28 immunological non-responders (INRs) (≥500 and <200 cluster of differentiation (CD)4+ T-cell counts/µL after 2 years of HIV-1 suppression, respectively) with no comorbidities. Plasma samples were used to measure the circulating levels of MT markers. All enrolled study participants had received 2 years of viral-suppression therapy. Results: Levels of lipopolysaccharide (P = 0.0185), LPS-binding protein (P < 0.0001), soluble-CD14 (P < 0.0001), and endogenous endotoxin-core antibody (P < 0.0001) at baseline were significantly higher in INRs than in IRs and were associated with an increased risk of an immunological non-response, whereas the level of intestinal fatty acid-binding protein did not show this association. Analysis of receiver operating characteristic (ROC) curves demonstrated the utility of these individual microbial markers in discriminating INRs after ART in people living with HIV with high sensitivity, specificity, and area under the ROC curve. Conclusion: INRs in HIV infection are characterized by increased MT at baseline. These markers could be used as a rapid prognostic tool for predicting immune responses in people infected with the HIV.
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Introduction: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been posing a severe threat to global public health. Although broadly neutralizing antibodies have been used to prevent or treat corona virus disease 2019 (COVID-19), new emerging variants have been proven resistant to these antibodies. Methods: In this study, we isolated receptor binding domain (RBD)-specific memory B cells using single-cell sorting method from two COVID-19 convalescents and expressed the antibody to test their neutralizing activity against diverse SARS-CoV-2 variants. Then, we resolved antibody-RBD complex structures of potent RBD-specific neutralizing antibodies by X-ray diffraction method. Finally, we analyzed the whole antibody repertoires of the two donors and studied the evolutionary pathway of potent neutralizing antibodies. Results and discussion: We identified three potent RBD-specific neutralizing antibodies (1D7, 3G10 and 3C11) from two COVID-19 convalescents that neutralized authentic SARS-CoV-2 WH-1 and Delta variant, and one of them, 1D7, presented broadly neutralizing activity against WH-1, Beta, Gamma, Delta and Omicron authentic viruses. The resolved antibody-RBD complex structures of two antibodies, 3G10 and 3C11, indicate that both of them interact with the external subdomain of the RBD and that they belong to the RBD-1 and RBD-4 communities, respectively. From the antibody repertoire analysis, we found that the CDR3 frequencies of the light chain, which shared high degrees of amino acid identity with these three antibodies, were higher than those of the heavy chain. This research will contribute to the development of RBD-specific antibody-based drugs and immunogens against multiple variants.
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COVID-19 , SARS-CoV-2 , Humanos , Anticuerpos ampliamente neutralizantes , Anticuerpos NeutralizantesRESUMEN
Abnormal oxidative stress caused by human immunodeficiency virus (HIV) infection affects viral replication and causes non-acquired immune deficiency syndrome-related complications in infected individuals. The transcription factor NFE2-related factor 2 (NRF2), a key regulator of oxidative stress, responds to abnormal oxidative stress by regulating the expression of NRF2-dependent cytoprotective genes. The present study aimed to determine whether inhibition of oxidative stress could control HIV replication and improve cell survival. In this study, the NRF2 activator, methyl bardoxolone, was used to treat cells for HIV infection. The effects on HIV replication and apoptosis pathways were confirmed by NRF2 activation or knockdown. The results showed that NRF2 activation could block HIV replication in macrophages before the integration phase and inhibited the expression of apoptotic pathways in virus-exposed macrophages. The study presents an unconventional anti-viral strategy of activation antioxidant response for HIV infection blocking.
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Autoimmune hepatitis (AIH) affects all age group and occurs mainly in women. Pyroptosis is a novel programmed cell death featured with cell bursting and release of proinflammatory cytokines. A deeper understanding of AIH pathogenesis will contribute to novel therapy for AIH patients. Here, we aimed to investigate the role of IL-17 in immune-mediated liver injury. The levels of cytokines were measured by ELISA, and mRNA levels of STAT3 and IFN gamma-inducible protein 16 (IFI16) were detected by PCR. Expressions of STAT3, IFI16, gasdermin D and cleaved caspase-1 were measured by western-blotting. Immunohistochemical staining and transmission electron microscopy were applied to evaluate liver histopathological changes of the treated mice. Our results showed that the levels of IFI16 was increased in hepatocytes treated with IL-17 protein, and further elevated after STAT3-overexpressed (STAT3-OE) lentivirus treatment. The levels of IFI16 were reduced in hepatocytes treated with IL-17 neutralizing Ab (nAb), but were significantly increased after STAT3-OE treatment. Pyroptosis was observed in hepatocytes treated with IL-17 protein, and further cell damage was observed after STAT3-OE lentivirus treatment. Liver damage was alleviated in mice treated with IL-17 nAb, however sever damage was experienced after STAT3-OE lentivirus treatment. A binding interaction between IFI16 and STAT3 was detected in IL-17 treated hepatocytes. Glutathione transaminase activity was enhanced in concanavalin A-induced AIH mice compared to the control group (p<0.01). IL-17 plays an important role in activating STAT3 and up-regulating IFI16, which may promote the pyroptosis in AIH-related liver injury through STAT3-IFI16 axis.
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Therapeutic and diagnostic efficacies of small biomolecules and chemical compounds are hampered by suboptimal pharmacokinetics. Here, we developed a repertoire of robust and high-affinity antihuman serum albumin nanobodies (NbHSA) that can be readily fused to small biologics for half-life extension. We characterized the thermostability, binding kinetics, and cross-species reactivity of NbHSAs, mapped their epitopes, and structurally resolved a tetrameric HSA-Nb complex. We parallelly determined the half-lives of a cohort of selected NbHSAs in an HSA mouse model by quantitative proteomics. Compared to short-lived control nanobodies, the half-lives of NbHSAs were drastically prolonged by 771-fold. NbHSAs have distinct and diverse pharmacokinetics, positively correlating with their albumin binding affinities at the endosomal pH. We then generated stable and highly bioactive NbHSA-cytokine fusion constructs "Duraleukin" and demonstrated Duraleukin's high preclinical efficacy for cancer treatment in a melanoma model. This high-quality and versatile Nb toolkit will help tailor drug half-life to specific medical needs.
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There is a worldwide pandemic of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; yet our understanding remains limited on the characteristic of antibodies, especially for dynamic long-term tracking. Sequential serum samples were collected up to 416 days post onset of symptoms (POS) from 102 patients who were hospitalized with coronavirus disease 2019 (COVID-19). Immunoglobulin (Ig)G, IgM, and IgA levels targeting SARS-CoV-2 spike 1 receptor-binding domain (S1-RBD), spike 2 extracellular domain (S2-ECD), and nucleocapsid protein (N) were quantified as well as neutralizing activity. We were pleasantly surprised to find that the antibody remained detective and effective for more than a year POS. We also found the varied reactions of different antibodies as time passed: N-IgA rose most rapidly in the early stage of infection, while S2-IgG was present at a high level in the long time of observation. This study described the long traceable antibody response of the COVID-19 and offered hints about targets to screen for postinfectious immunity and for vaccination development of SARS-CoV-2.
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Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/inmunología , SARS-CoV-2/inmunología , Anciano , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/diagnóstico , Proteínas de la Nucleocápside de Coronavirus/inmunología , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Isotipos de Inmunoglobulinas/sangre , Isotipos de Inmunoglobulinas/inmunología , Cinética , Masculino , Persona de Mediana Edad , Modelos Teóricos , Fosfoproteínas/inmunología , Dominios Proteicos/inmunología , SARS-CoV-2/aislamiento & purificación , Seroconversión , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
Viral DNA integrated in host cells is a major barrier to completely curing HIV-1. However, genome editing using the recently developed technique of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 has the potential to eradicate HIV-1. The present study aimed to use a lentiviral vector-based CRISPR/Cas9 system combined with dual-small/single guide RNAs (sgRNAs) to attack HIV-1 DNA in the latency reactivation model J-Lat 10.6 cell line and to assess off-target effects using whole-genome sequencing (WGS). We designed 12 sgRNAs targeting HIV-1 DNA, and selected high-efficiency sgRNAs for further pairwise combinations after a preliminary evaluation of the editing efficiency. Three combinations of dual-sgRNAs/Cas9 with high editing efficiency were screened successfully from multiple combinations. Among these combinations, the incidences of insertions and deletions in the sgRNA-targeted regions reached 76% and above, and no credible off-target sites were detected using WGS. The results provided comprehensive basic experimental evidence and methodological recommendations for future personalized HIV-1 treatment using CRISPR/Cas9 genome editing technology.
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BACKGROUND: In 2020, a new coronavirus, SARS-CoV-2, quickly spread worldwide within a few months. Although coronaviruses typically infect the upper or lower respiratory tract, the virus RNA can be detected in plasma. The risk of transmitting coronavirus via transfusion of blood products remains. As more asymptomatic infections are identified in COVID-19 cases, blood safety has become particularly important. Methylene blue (MB) photochemical technology has been proven to inactivate lipid-enveloped viruses with high efficiency and safety. The present study aimed to investigate the SARS-CoV-2 inactivation effects of MB in plasma. METHODS: The SARS-CoV-2 virus strain was isolated from Zhejiang University. The live virus was harvested from cultured VERO-E6 cells, and mixed with MB in plasma. The MB final concentrations were 0, 1, 2, and 4 µM. The "BX-1 AIDS treatment instrument" was used at room temperature, the illumination adjusted to 55,000 ± 0.5 million Lux, and the plasma was irradiated for 0, 2, 5, 10, 20, and 40 mins using light at a single wavelength of 630 nm. Virus load changes were measured using quantitative reverse transcription- PCR. RESULTS: BX-1 could effectively eliminate SARS-CoV-2 within 2 mins in plasma, and the virus titer declined to 4.5 log10 TCID50 (median tissue culture infectious dose)/mL. CONCLUSION: BX-1 is based on MB photochemical technology, which was designed to inactivate HIV-1 virus in plasma. It was proven to be safe and reliable in clinical trials of HIV treatment. In this study, we showed that BX-1 could also be applied to inactivate SARS-CoV-2. During the current outbreak, this technique it has great potential for ensuring the safety of blood transfusions, for plasma transfusion therapy in recovering patients, and for preparing inactivated vaccines.
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Seguridad de la Sangre , COVID-19/prevención & control , COVID-19/terapia , Azul de Metileno/farmacología , SARS-CoV-2/efectos de los fármacos , Inactivación de Virus , Animales , Transfusión Sanguínea , Chlorocebus aethiops , Humanos , Inmunización Pasiva , Plasma/virología , ARN Viral , Células Vero , Sueroterapia para COVID-19RESUMEN
MicroRNAs (miRNAs) are important host molecules involved in human immunodeficiency virus type 1 (HIV-1) infection. Antiretroviral therapy (ART) can affect the miRNA expression profile, but differentially expressed miRNAs still remain to be identified. In this study, we used gene chips to analyze miRNA expression profiles in peripheral blood mononuclear cells from ART-naive HIV-1 patients and those receiving ART, as well as from uninfected individuals. We measured differences in miRNA expression by quantitative polymerase chain reaction (qPCR) in an expanded sample. We found significant differences in the expression of has-miR-191-5p among the three groups (P < 0.05). Furthermore, we showed that hsa-miR-191-5p has an inhibitory effect on HIV-1 replication in cell models in vitro. We identified CCR1 and NUP50 as target molecules of hsa-miR-191-5p and found that hsa-miR-191-5p inhibits the expression of CCR1 and NUP50. Knockdown of NUP50 resulted in significant inhibition of HIV-1 replication. In summary, our research shows that hsa-miR-191-5p expression is reduced in HIV-1-infected patients and acts an inhibitor of HIV-1 infection via a mechanism that may involve targeted repression of NUP50 expression.
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Regulación de la Expresión Génica/genética , VIH-1/metabolismo , MicroARNs/genética , Proteínas de Complejo Poro Nuclear/biosíntesis , Proteínas Nucleares/biosíntesis , Receptores CCR1/biosíntesis , Adulto , Línea Celular , Regulación hacia Abajo , Femenino , Perfilación de la Expresión Génica , Células HEK293 , Humanos , Células Jurkat , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa , Replicación Viral/genética , Adulto JovenRESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally with more than 33 million patients diagnosed, taking more than a million lives. Abundant mutations were observed but the functional consequences of these mutations are largely unknown. We report the mutation spectrum, replication dynamics, and infectivity of 11 patient-derived viral isolates in diverse cell lines, including the human lung cancer cell line Calu-3. We observed 46 mutations, including 9 different mutations in the spike gene. Importantly, these viral isolates show significant and consistent variations in replication dynamics and infectivity in tested cell lines, up to a 1500-fold difference in viral titers at 24 h after infecting Calu-3 cells. Moreover, we show that the variations in viral titers among viral isolates are positively correlated with blood clotting function but inversely correlated with the amount of red blood cell and hemoglobin in patients. Therefore, we provide direct evidence that naturally occurring mutations in SARS-CoV-2 can substantially change its replication dynamics and infectivity in diverse human cell lines, with clinical implications in vivo.
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The mutations in the SARS-CoV-2 virus genome during COVID-19 dissemination are unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases compared with patients in Wuhan. For mechanisms exploration, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified. Phylogenetic and relative synonymous codon usage analysis suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 global virus strains based on the base (C or T) at positions 8824 and 28247 while ZJ01 has T at both sites. The prediction of the Furin cleavage site (FCS) and sequence alignment indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was especially higher in glands, liver, kidneys, and colon. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 caused mild flu-like symptoms, further showing its potential in differentiating into mild COVID-19 subtypes.
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Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Furina/metabolismo , Neumonía Viral/virología , Adulto , Betacoronavirus/genética , COVID-19 , China/epidemiología , Codón , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Progresión de la Enfermedad , Evolución Molecular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pandemias , Filogenia , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Análisis de Secuencia de ARNRESUMEN
Sterile α motif and histidine/aspartic acid domaincontaining protein 1 (SAMHD1) can inhibit reverse transcription of human immunodeficiency virus1 (HIV1) by hydrolyzing intracellular deoxyribonucleoside triphosphate. However, its role in HIV1 disease progression has not been extensively studied. To study the impacts of SAMHD1 on HIV1 disease progression, especially on DNA levels, we investigated SAMHD1 levels in the peripheral blood of HIV1 elite controllers (ECs), antiretroviral therapy (ART) naive viremic progressors (VPs) and patients with HIV1 receiving ART (HIVARTs) compared with healthy controls. In addition, the present study analyzed the relationship between SAMHD1 and interferonα, immune activation and HIV1 DNA levels. The results of the present study demonstrated elevated SAMHD1 expression in the peripheral blood mononuclear cells of all patients withHIV1, but higher SAMHD1 expression in the CD4+ T cells of only ECs compared with healthy controls. Immune activation was increased in the VPs and decreased in the ECs compared with healthy controls. Substantially lower HIV1 DNA levels were identified in ECs compared with those in VPs and HIVARTs. SAMHD1 expression was associated with low levels of immune activation. No significant correlation was observed between SAMHD1 and HIV1 DNA levels. Overall, the findings of the present study indicated that SAMHD1 was highly expressed in ECs, which may be associated with low immune activation levels, but was not directly related to HIV1 DNA levels.
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Linfocitos T CD4-Positivos/química , Linfocitos T CD4-Positivos/inmunología , ADN Viral/sangre , Infecciones por VIH/inmunología , VIH-1/química , Proteína 1 que Contiene Dominios SAM y HD/sangre , Proteína 1 que Contiene Dominios SAM y HD/inmunología , Adulto , Antirretrovirales/uso terapéutico , Femenino , Regulación Enzimológica de la Expresión Génica , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , VIH-1/genética , Humanos , Interferón-alfa/sangre , Leucocitos Mononucleares/química , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Proteína 1 que Contiene Dominios SAM y HD/genética , Carga ViralRESUMEN
Currently, there are three algorithms for screening of syphilis: traditional algorithm, reverse algorithm and European Centre for Disease Prevention and Control (ECDC) algorithm. To date, there is not a generally recognized diagnostic algorithm. When syphilis meets HIV, the situation is even more complex. To evaluate their screening performance and impact on the seroprevalence of syphilis in HIV-infected individuals, we conducted a cross-sectional study included 865 serum samples from HIV-infected patients in a tertiary hospital. Every sample (one per patient) was tested with toluidine red unheated serum test (TRUST), T. pallidum particle agglutination assay (TPPA), and Treponema pallidum enzyme immunoassay (TP-EIA) according to the manufacturer's instructions. The results of syphilis serological testing were interpreted following different algorithms respectively. We directly compared the traditional syphilis screening algorithm with the reverse syphilis screening algorithm in this unique population. The reverse algorithm achieved remarkable higher seroprevalence of syphilis than the traditional algorithm (24.9% vs. 14.2%, p < 0.0001). Compared to the reverse algorithm, the traditional algorithm also had a missed serodiagnosis rate of 42.8%. The total percentages of agreement and corresponding kappa values of tradition and ECDC algorithm compared with those of reverse algorithm were as follows: 89.4%,0.668; 99.8%, 0.994. There was a very good strength of agreement between the reverse and the ECDC algorithm. Our results supported the reverse (or ECDC) algorithm in screening of syphilis in HIV-infected populations. In addition, our study demonstrated that screening of HIV-populations using different algorithms may result in a statistically different seroprevalence of syphilis.
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Algoritmos , Infecciones por VIH/complicaciones , Tamizaje Masivo/métodos , Pruebas Serológicas/métodos , Sífilis/diagnóstico , Sífilis/epidemiología , Treponema pallidum/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Centros de Atención Terciaria , Adulto JovenRESUMEN
The differentiation and response ofCD8+ T cells is vital in host defense against human immunodeficiency virus type 1 (HIV-1). MicroRNA (miR)155 is an important regulator of T cell differentiation. However, the profile of miR-155 in HIV1 infected individuals and its association with CD8+ T cell differentiation remain to be fully elucidated. The present crosssectional study was performed involving 63 HIV1infected patients undergoing highly active antiretroviral therapy (HAART), 31 HAARTnaïve patients and 35 healthy controls. The levels of miR155 in CD8+ T cells were detected using reverse transcriptionquantitative polymerase chain reaction analysis. Subsets of CD8+ T cell differentiation were detected using flow cytometry. The results revealed that the discord controllers and HAARTnaïve patients showed higher percentages of effector and effector memory cells, and lower percentages of naïve cells (P<0.05). The levels of miR155 in CD8+ T cells from the HIV1infected patients were higher, particularly in the discord controllers and HAART naïve patients (P<0.01). The expression levels of miR155 were positively correlated with the percentages of effector and effector memory CD8+ T cells, and negatively correlated with the percentages of naïve and central memory CD8+ T cells (P<0.01). Taken together, these findings suggested that the levels of miR155 in CD8+ T cells of patients with HIV-1 were increased and asso-ciated with CD8+ T cell differentiation.
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Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Infecciones por VIH/genética , VIH-1/inmunología , MicroARNs/biosíntesis , Adulto , Terapia Antirretroviral Altamente Activa , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/metabolismo , Diferenciación Celular/fisiología , Estudios Transversales , Femenino , Citometría de Flujo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Memoria Inmunológica , Activación de Linfocitos/inmunología , Masculino , MicroARNs/genética , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Carga ViralRESUMEN
MicroRNAs are potent gene expression regulators involved in regulating various biological processes, including host-pathogen interactions. In this study, we used high-throughput sequencing to investigate cellular miRNA signatures related to HIV-1 replication and latent infection in CD4+ T cell lines, which included HIV-1-replicating H9/HTLV-IIIB, HIV-1-latently-infected CEM-Bru cells, and their parental uninfected H9 and CEM-SS cells. Relatively few miRNAs were found to be modulated by HIV-1 replication or latent infection, while the cell-lineage-specific miRNA difference was more pronounced, irrespective of HIV-1 infection. In silico analysis showed that some of our HIV-1 infection-regulated miRNA profiles echoed previous studies, while others were novel. In addition, some of the miRNAs that were differentially expressed between the productively and latently infected cells seemed to participate in shaping the differential infection state. Thus, the newly identified miRNA profiles related to HIV-1 replication and latency provide information about the interplay between HIV-1 and its host.
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Linfocitos T CD4-Positivos/virología , VIH-1/genética , VIH-1/fisiología , MicroARNs/genética , Latencia del Virus/fisiología , Replicación Viral/fisiología , Línea Celular Tumoral , Humanos , MicroARNs/fisiología , ARN Viral/aislamiento & purificaciónRESUMEN
The available evidence suggests that alterations in gut microbiota may be tightly linked to the increase in microbial translocation and systemic inflammation in patients with human immunodeficiency virus 1 (HIV-1) infection. We profiled the fecal microbiota as a proxy of gut microbiota by parallel barcoded 454-pyrosequencing in 67 HIV-1-infected patients (32 receiving highly active antiretroviral therapy [HAART] and 35 HAART naïve) and 16 healthy controls from a Chinese population. We showed that α-diversity indices did not differ significantly between the healthy control and HIV-1-infected patients. The ratio of Firmicutes/Bacteroidetes increased significantly in HIV-1-infected patients. Several key bacterial phylotypes, including Prevotella, were prevalent in HIV-1-infected patients; whereas Phascolarctobacterium, Clostridium XIVb, Dialister and Megamonas were significantly correlated with systemic inflammatory cytokines. After short-term, effective HAART, the viral loads of HIV-1 were reduced; however, the diversity and composition of the fecal microbiota were not completely restored. and the dysbiosis remained among HIV-1-infected subjects undergoing HAART. Our detailed analysis demonstrated that dysbiosis of fecal microbiota might play an active role in HIV-1 infection. Thus, new insights may be provided into therapeutics that target the microbiota to attenuate the progression of HIV disease and to reduce the risk of gut-linked disease in HIV-1-infected patients.
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Disbiosis , Heces/microbiología , Infecciones por VIH/complicaciones , Microbiota , Antirretrovirales/uso terapéutico , Pueblo Asiatico , Código de Barras del ADN Taxonómico , Infecciones por VIH/tratamiento farmacológico , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: Diabetes mellitus (DM) is common in human immunodeficiency virus (HIV)-infected patients. However, the relationship between dysglycemia, lipid metabolism, and immune activation in HIV patients is poorly understood. METHODS: We retrospectively analyzed the clinical data of 180 HIV patients, including 153 patients undergoing highly active antiretroviral therapy (HAART) and 27 HAART-naive patients. DM was defined as fasting serum glucose levels ≥126 mg/dl, and impaired fasting glucose (IFG) was defined as serum glucose levels of 101-125 mg/dl at two different time points. Lipid metabolic indexes were measured. CD4+, CD8+, and CD8+ HLA-DR+ T cells were determined by flow cytometry. RESULTS: IFM and DM percentages were higher in the HAART group than in the HAART-naive group (59.5% vs. 48.1% and 21.6% vs. 7.4%, respectively; p < 0.01). Additionally, DM percentage was high in patients receiving HAART containing protease inhibitors. Serum levels of triglycerides and very low-density lipoprotein cholesterol were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Serum triglyceride levels were higher in HAART-naive DM patients than in other patients (p < 0.05). CD8+ and CD8+ HLA-DR+ cell counts were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Ordinal logistic regression analysis suggested that TRIG, VLDL, CD8, and HAART were predictors of glucose metabolic disorders. CONCLUSION: HIV patients with hyperglycemia have severe dyslipidemia and immune activation, and HAART is an important impact factor of glucose and lipid metabolic disorders.
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Glucemia , Dislipidemias/etiología , Dislipidemias/metabolismo , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , Activación de Linfocitos , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/efectos adversos , Biomarcadores , Recuento de Linfocito CD4 , Dislipidemias/diagnóstico , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Carga ViralRESUMEN
Thyroid dysfunction is more common in human immunodeficiency virus (HIV) patients. But the effects of highly active antiretroviral therapy (HAART) and hepatitis B/C virus (HBV/HCV) coinfection on thyroid function is unclear. We retrospectively reviewed the data of 178 HIV patients and determined the prevalence of thyroid dysfunction and the relationship between thyroid hormone levels, CD4 cell count, HIV-1 duration, HAART duration/regimens, and HBV/HCV coinfection. Of the 178 patients, 59 (33.1%) had thyroid dysfunction, mostly hypothyroidism. Thyroid dysfunction was significantly more frequent in the HAART group (41/104, 39.4%) than in the HAART-naïve group (18/74, 24.3%; P < 0.05). The mean CD4 cell count was significantly lower in patients with hypothyroidism (372 ± 331/µL) than in the other patients (P < 0.05). The FT4 level was significantly lower in the HAART group than in the HAART-naïve group (1.09 ± 0.23 versus 1.20 ± 0.29 pg/mL, P < 0.05). FT3/FT4 levels were negatively related to HIV duration and FT3 levels were positively related to CD4 cell (P < 0.05). HBV patients had lower FT3 levels, while HCV patients had higher FT3 and FT4 levels (P < 0.05). Thyroid dysfunction is more common in HIV patients on HAART, mainly manifested as hypothyroidism. FT3/FT4 levels are correlated with HIV progression. HBV/HCV coinfection increases the probability of thyroid dysfunction.