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PLoS Pathogens Jun 2024Understanding the mechanisms that drive HIV expression and latency is a key goal for achieving an HIV cure. Here we investigate the role of the SETD2 histone...
Understanding the mechanisms that drive HIV expression and latency is a key goal for achieving an HIV cure. Here we investigate the role of the SETD2 histone methyltransferase, which deposits H3K36 trimethylation (H3K36me3), in HIV infection. We show that prevention of H3K36me3 by a potent and selective inhibitor of SETD2 (EPZ-719) leads to reduced post-integration viral gene expression and accelerated emergence of latently infected cells. CRISPR/Cas9-mediated knockout of SETD2 in primary CD4 T cells confirmed the role of SETD2 in HIV expression. Transcriptomic profiling of EPZ-719-exposed HIV-infected cells identified numerous pathways impacted by EPZ-719. Notably, depletion of H3K36me3 prior to infection did not prevent HIV integration but resulted in a shift of integration sites from highly transcribed genes to quiescent chromatin regions and to polycomb repressed regions. We also observed that SETD2 inhibition did not apparently affect HIV RNA levels, indicating a post-transcriptional mechanism affecting HIV expression. Viral RNA splicing was modestly reduced in the presence of EPZ-719. Intriguingly, EPZ-719 exposure enhanced responsiveness of latent HIV to the HDAC inhibitor vorinostat, suggesting that H3K36me3 can contribute to a repressive chromatin state at the HIV locus. These results identify SETD2 and H3K36me3 as novel regulators of HIV integration, expression and latency.
Topics: Histone-Lysine N-Methyltransferase; Humans; Virus Latency; HIV Infections; HIV-1; CD4-Positive T-Lymphocytes; Gene Expression Regulation, Viral
PubMed: 38848441
DOI: 10.1371/journal.ppat.1012281 -
Journal of AIDS and HIV Treatment 2024This review underscores the important role of nutrition in enhancing the management of Human Immunodeficiency Virus type 1 (HIV-1). Highlighting the efficacy of dietary...
This review underscores the important role of nutrition in enhancing the management of Human Immunodeficiency Virus type 1 (HIV-1). Highlighting the efficacy of dietary interventions, including, the importance of omega-3 fatty acids, vitamins D and B-12, and the Mediterranean diet, we delineate how these beneficial nutritional strategies can improve the effectiveness of combined antiretroviral therapy (cART), mitigate its side effects, and ameliorate metabolic disorders in people living with HIV-1 (PLWH). Our review advocates for the integration and implementation of personalized nutritional assessments into the care plan for PLWH, proposing actionable strategies for healthcare providers in HIV-1 field. Summarizing the current standing of the relevance of the nutritional and well-planned diet recommended for the PLWH and emphasizing on the future research directions, this review establishes a foundation for nutrition as a cornerstone in comprehensive HIV-1 management. Our review aims to improve patients' health outcomes and overall quality of life for PLWH.
PubMed: 38845818
DOI: 10.33696/aids.6.048 -
Journal of Affective Disorders Jun 2024Immunity alterations have been observed in bipolar disorder (BD). However, whether serum positivity of antibodies to Toxoplasma gondii (T gondii), rubella, and...
BACKGROUND AND AIM
Immunity alterations have been observed in bipolar disorder (BD). However, whether serum positivity of antibodies to Toxoplasma gondii (T gondii), rubella, and cytomegalovirus (CMV) shared clinical relevance with BD, remains controversial. This study aimed to investigate this association.
METHODS
Antibody seropositivity of IgM and IgG to T gondii, rubella virus, and CMV of females with BD and controls was extracted based on medical records from January 2018 to January 2023. Family history, type of BD, onset age, and psychotic symptom history were also collected.
RESULTS
585 individuals with BD and 800 healthy controls were involved. Individuals with BD revealed a lower positive rate of T gondii IgG in the 10-20 aged group (OR = 0.10), and a higher positive rate of rubella IgG in the 10-20 (OR = 5.44) and 20-30 aged group (OR = 3.15). BD with family history preferred a higher positive rate of T gondii IgG (OR = 24.00). Type-I BD owned a decreased positive rate of rubella IgG (OR = 0.37) and an elevated positive rate of CMV IgG (OR = 2.12) compared to type-II BD, while BD with early onset showed contrast results compared to BD without early onset (Rubella IgG, OR = 2.54; CMV IgG, OR = 0.26). BD with psychotic symptom history displayed a lower positive rate of rubella IgG (OR = 0.50).
LIMITATIONS
Absence of male evidence and control of socioeconomic status and environmental exposure.
CONCLUSIONS
Differential antibody seropositive rates of T gondii, rubella, and cytomegalovirus in BD were observed.
PubMed: 38844171
DOI: 10.1016/j.jad.2024.06.014 -
Pest Management Science Jun 2024Asian citrus psyllid, Diaphorina citri, is a hemipteran that vectors the causal pathogen of citrus greening disease, or huanglongbing (HLB). HLB is a tree killing...
BACKGROUND
Asian citrus psyllid, Diaphorina citri, is a hemipteran that vectors the causal pathogen of citrus greening disease, or huanglongbing (HLB). HLB is a tree killing disease that has severely limited citrus production globally. Unfortunately, there is no cure for this disease, and mitigation depends on multiple insecticide applications to reduce vector populations. Silencing of cytochrome P expression associated with detoxification enzymes by RNA interference is known to increase susceptibility of D. citri to insecticides. However, dsRNA was previously introduced into psyllids by topical applications. The possible application of this technology for pest management will require effective field delivery of the dsRNA. Therefore, we evaluated a virus vector (Citrus tristeza virus; 'mild strain' T36) to deliver gene silencing directly to this sap-sucking insect via plant phloem. Citrus macrophylla plants inoculated with CTV expressing a truncated consensus sequence of CYP (CTV-tCYP) constantly produced small interfering RNA in the plant phloem that targeted five cytochrome p540 (CYP) genes in D. citri.
RESULTS
Insecticide susceptible D. citri reared on citrus infected with CTV-tCYP were subsequently more susceptible to imidacloprid, fenpropathrin, carbaryl, and chlorpyrifos than those reared on citrus infected with wildtype CTV or non-infected negative controls. Additionally, nymph survival and adult lifespan were significantly reduced when psyllids were reared on CTV-tCYP citrus plants compared with controls. Interestingly, similar results were obtained after one and two generations of rearing. Finally, field-collected psyllids from areas with known broad-spectrum insecticide resistance were rendered more susceptible to imidacloprid and fenpropathrin after feeding on CTV-tCYP citrus trees as compared with those reared on controls.
CONCLUSION
The integration of citrus-mediated RNA inference targeting psyllid detoxification enzymes could function as a resistance management tool and reduce insecticide input in an integrated pest management program for HLB. © 2024 Society of Chemical Industry.
PubMed: 38843443
DOI: 10.1002/ps.8218 -
Voprosy Virusologii May 2024The HTLV-1 infection persists for life, remaining as asymptomatic viral reservoirs in most patients, ensuring the chain of transmission, but around 4% develop adult...
OBJECTIVES
The HTLV-1 infection persists for life, remaining as asymptomatic viral reservoirs in most patients, ensuring the chain of transmission, but around 4% develop adult T-cell leukemia/lymphoma (ATLL). HTLV-1 is an oncogenic retrovirus that transforms CD4 T lymphocytes and deregulates the lymphoproliferative pathways that contribute to the development of ATLL. To achieve cell transformation, most oncogenic retroviruses use proto-oncogene capture transduction, with proviral integration disrupting the expression of tumor suppressors or proto-oncogenes.
THE AIM
We conducted this study on the prevalence of HTLV-1 infection in blood donors to expand the HTLV-1 database, assess the risk of transmission via blood products, as well as evaluate the risk of persistent infection or development of neoplastic diseases in HTLV-1 carriers.
MATERIALS AND METHODS
This is a cross-sectional study of blood donors of all categories. For this study, 265 blood donors were recruited at the Centre National de Transfusion Sanguine in Brazzaville. After testing for HTLV-1 antibodies by ELISA, proviral DNA was extracted from all ELISA-positive samples for detection by nested PCR, followed by RT qPCR using specific primers p53 and c-myc for gene expression.
RESULTS
20/265 were positive for anti-HTLV-1 antibody, 5 donors were positive for proviral DNA. The prevalence of HTLV-1 was 1.8%. All HTLV-1-positive donors were male (1.8%), with a positive correlation ( = 0.05); the 1.1% of positive donors were regular, with the majority aged between 31 and 45 years (1.5%), and concubine donors were the most frequent (1.1%). All samples showed normal expression of the and genes.
CONCLUSION
The prevalence, though low, remains a serious problem. No abnormal orgene expression was detected in HTLV-1-positive donors, which could mean that none of the T lymphocytes in these donors had been transformed by HTLV-1.
Topics: Humans; Human T-lymphotropic virus 1; Male; Blood Donors; HTLV-I Infections; Adult; Female; Tumor Suppressor Protein p53; Middle Aged; Proto-Oncogene Proteins c-myc; Proto-Oncogene Mas; Cross-Sectional Studies; Gene Expression Profiling; Leukemia-Lymphoma, Adult T-Cell; Proviruses; Adolescent
PubMed: 38843019
DOI: 10.36233/0507-4088-199 -
BMJ Open Jun 2024Migrants from high HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) endemicity regions have a great burden of these infections and related diseases in the host... (Observational Study)
Observational Study
OBJECTIVES
Migrants from high HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) endemicity regions have a great burden of these infections and related diseases in the host countries. This study aimed to assess the predictive capacity of the Test Rapide d'Orientation Diagnostique (TROD) Screen questionnaire for HIV, HBV and HCV infections among migrants arriving in France.
DESIGN
An observational and multicentre study was conducted among migrants. A self-questionnaire on demographic characteristics, personal medical history and sexual behaviours was completed.
SETTING
The study was conducted in the centres of the French Office for Immigration and Integration (OFII).
PARTICIPANTS
Convenience sampling was used to select and recruit adult migrants between January 2017 and March 2020.
OUTCOME MEASURES
Participants were tested for HIV, HBV and HCV with rapid tests. For each infection, the test performance was assessed using receiver operating characteristics curves, using area under the curve (AUC) as a measure of accuracy.
RESULTS
Among 21 133 regular migrants seen in OFII centres, 15 343 were included in the study. The participants' mean age was 35.6 years (SD±11.1). The prevalence (95% CI) of HBV, HCV and HIV was 2.0% (1.8% to 2.2%), 0.3% (0.2% to 0.4%) and 0.3% (0.2% to 0.4%), respectively. Based on the sensitivity-specificity curve analysis, the cut-off points (95% CI) chosen for the risk score were: 2.5 (2.5 to 7.5) for HBV infection in men; 6.5 (0.5 to 6.5) for HBV infection in women; 9.5 (9.5 to 12.5) for HCV infection; and 10.5 (10.0 to 18.5) for HIV infection. Test performance was highest for HIV (AUC=82.15% (95% CI 74.54% to 87.99%)), followed by that for HBV in men (AUC=79.22%, (95% CI 76.18% to 82.26%)), for HBV in women (AUC=78.83 (95% CI 74.54% to 82.10%)) and that for HCV (AUC=75.95% (95% CI 68.58% to 83.32%)).
CONCLUSION
The TROD screen questionnaire showed good overall performance for predicting HIV, HBV and HCV infections among migrants in OFII centres. It could be used to optimise screening for these infections and to propose rapid screening tests to those who are at high risk.
TRIAL REGISTRATION NUMBER
NCT02959684.
Topics: Humans; Male; Female; Adult; HIV Infections; France; Hepatitis C; Hepatitis B; Transients and Migrants; Mass Screening; Middle Aged; Risk Assessment; ROC Curve; Surveys and Questionnaires; Prevalence
PubMed: 38839381
DOI: 10.1136/bmjopen-2023-075315 -
Lancet Regional Health. Americas Jul 2024Few studies have evaluated the effects of the Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, on maternal and perinatal health at a...
Maternal and perinatal health indicators in Brazil over a decade: assessing the impact of the COVID-19 pandemic and SARS-CoV-2 vaccination through interrupted time series analysis.
BACKGROUND
Few studies have evaluated the effects of the Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, on maternal and perinatal health at a populational level. We investigated maternal and perinatal health indicators in Brazil, focusing on the effects of the COVID-19 pandemic, and SARS-CoV-2 vaccination campaign for pregnant women.
METHODS
Utilizing interrupted time series analysis (January 2013-December 2022), we examined Maternal Mortality Ratio, Perinatal Mortality Rate, Preterm Birth Rate, Cesarean Section Rate, and other five indicators. Interruptions occurred at the pandemic's onset (March 2020) and pregnant women's vaccination (July 2021). Results were expressed as percent changes on time series' level and slope.
FINDINGS
The COVID-19 onset led to immediate spikes in Maternal Mortality Ratio (33.37%) and Perinatal Mortality Rate (3.20%) (p < 0.05). From March 2020 to December 2022, Cesarean Section and Preterm Birth Rates exhibited upward trends, growing monthly at 0.13% and 0.23%, respectively (p < 0.05). Post start of SARS-CoV-2 vaccination (July 2021), Maternal Mortality Ratio (-34.10%) and Cesarean Section Rate (-1.87%) promptly declined (p < 0.05). Subsequently, we observed a monthly decrease of Maternal Mortality Ratio (-9.43%) and increase of Cesarean Section Rate (0.25%) (p < 0.05), while Perinatal Mortality Rate and Preterm Birth Rate showed a stationary pattern.
INTERPRETATION
The pandemic worsened all analyzed health indicators. Despite improvements in Maternal Mortality Ratio, following the SARS-CoV-2 vaccination campaign for pregnant women, the other indicators continued to sustain altered patterns from the pre-pandemic period.
FUNDING
No funding.
PubMed: 38828284
DOI: 10.1016/j.lana.2024.100774 -
HIV/AIDS (Auckland, N.Z.) 2024HIV-associated neurocognitive disorders (HAND) are becoming a significant public health concern in the continuum of human immune virus (HIV) treatment. These disorders...
Healthcare Workers' Perspectives on the Utilization of the International HIV Dementia Scale for the Screening HIV-Associated Neurocognitive Disorders: A Qualitative Study at TASO Centres in Central and Southwestern Uganda.
INTRODUCTION
HIV-associated neurocognitive disorders (HAND) are becoming a significant public health concern in the continuum of human immune virus (HIV) treatment. These disorders range from subtle cognitive impairments to severe dementia. Despite many early-stage HAND cases being asymptomatic, healthcare workers (HCWs) rarely perform routine neurocognitive assessments. This leads to a high number of unrecognized cases and increases the risk of HAND among people living with HIV (PLWH).
MATERIAL AND METHODS
We aimed to explore HCWs' perspectives on integrating the International HIV Dementia Scale (IHDS) into routine care for screening HAND at The AIDS Support Organization (TASO) centres in central and southwestern Uganda.
RESULTS
We conducted five focus group discussions with 37 HCWs from five TASO centres. Thematic analysis revealed eight key theme: 1) Impaired brain function, 2) Changes in activities of daily living, 3) Promotion of quality care perspectives, 4) Tool applicable and user-friendly, 5) Client increased self-awareness and self-confidence, 6) Integration of IHDS into routine HIV care, 7) Uncertainty about IHDS use, and 8) Continuous training for HCWs.
CONCLUSION
As PLWH enjoy longer and healthier lives, their risk for HAND increases, potentially affecting their quality of life. The use of the IHDS has raised awareness among HCWs and improved decision-making through cognitive assessments, emphasizing it value in PLWH. We recommend a prospective study to assess the long-term outcomes and efficacy of increased HAND screening. Furthermore, integrating a HAND screening module into the consolidated HIV guidelines is recommended to enhance its relevance.
PubMed: 38827783
DOI: 10.2147/HIV.S444668 -
Molecular Therapy. Methods & Clinical... Jun 2024Prenatal somatic cell gene therapy (PSCGT) could potentially treat severe, early-onset genetic disorders such as spinal muscular atrophy (SMA) or muscular dystrophy....
Prenatal somatic cell gene therapy (PSCGT) could potentially treat severe, early-onset genetic disorders such as spinal muscular atrophy (SMA) or muscular dystrophy. Given the approval of adeno-associated virus serotype 9 (AAV9) vectors in infants with SMA by the U.S. Food and Drug Administration, we tested the safety and biodistribution of AAV9-GFP (clinical-grade and dose) in fetal lambs to understand safety and efficacy after umbilical vein or intracranial injection on embryonic day 75 (E75) . Umbilical vein injection led to widespread biodistribution of vector genomes in all examined lamb tissues and in maternal uteruses at harvest (E96 or E140; term = E150). There was robust GFP expression in brain, spinal cord, dorsal root ganglia (DRGs), without DRG toxicity and excellent transduction of diaphragm and quadriceps muscles. However, we found evidence of systemic toxicity (fetal growth restriction) and maternal exposure to the viral vector (transient elevation of total bilirubin and a trend toward elevation in anti-AAV9 antibodies). There were no antibodies against GFP in ewes or lambs. Analysis of fetal gonads demonstrated GFP expression in female (but not male) germ cells, with low levels of integration-specific reads, without integration in select proto-oncogenes. These results suggest potential therapeutic benefit of AAV9 PSCGT for neuromuscular disorders, but warrant caution for exposure of female germ cells.
PubMed: 38827250
DOI: 10.1016/j.omtm.2024.101263 -
Scientific Reports May 2024Respiratory diseases, including influenza and coronaviruses, pose recurrent global threats. This study delves into the respiratory surveillance systems, focusing on the...
Respiratory diseases, including influenza and coronaviruses, pose recurrent global threats. This study delves into the respiratory surveillance systems, focusing on the effectiveness of SARI sentinel surveillance for total and severe cases incidence estimation. Leveraging data from the COVID-19 pandemic in Chile, we examined 2020-2023 data (a 159-week period) comparing census surveillance results of confirmed cases and hospitalizations, with sentinel surveillance. Our analyses revealed a consistent underestimation of total cases and an overestimation of severe cases of sentinel surveillance. To address these limitations, we introduce a nowcasting model, improving the precision and accuracy of incidence estimates. Furthermore, the integration of genomic surveillance data significantly enhances model predictions. While our findings are primarily focused on COVID-19, they have implications for respiratory virus surveillance and early detection of respiratory epidemics. The nowcasting model offers real-time insights into an outbreak for public health decision-making, using the same surveillance data that is routinely collected. This approach enhances preparedness for emerging respiratory diseases by the development of practical solutions with applications in public health.
Topics: Humans; COVID-19; Sentinel Surveillance; Chile; SARS-CoV-2; Pandemics; Incidence; Hospitalization
PubMed: 38822070
DOI: 10.1038/s41598-024-62965-5