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Immunity Mar 2023Upon infection, HIV disseminates throughout the human body within 1-2 weeks. However, its early cellular targets remain poorly characterized. We used a single-cell...
Upon infection, HIV disseminates throughout the human body within 1-2 weeks. However, its early cellular targets remain poorly characterized. We used a single-cell approach to retrieve the phenotype and TCR sequence of infected cells in blood and lymphoid tissue from individuals at the earliest stages of HIV infection. HIV initially targeted a few proliferating memory CD4 T cells displaying high surface expression of CCR5. The phenotype of productively infected cells differed by Fiebig stage and between blood and lymph nodes. The TCR repertoire of productively infected cells was heavily biased, with preferential infection of previously expanded and disseminated clones, but composed almost exclusively of unique clonotypes, indicating that they were the product of independent infection events. Latent genetically intact proviruses were already archived early in infection. Hence, productive infection is initially established in a pool of phenotypically and clonotypically distinct T cells, and latently infected cells are generated simultaneously.
Topics: Humans; HIV Infections; CD4-Positive T-Lymphocytes; HIV-1; Latent Infection; Receptors, Antigen, T-Cell; Virus Latency
PubMed: 36804957
DOI: 10.1016/j.immuni.2023.01.030 -
Viruses Jun 2022Herpesviruses are ubiquitous human pathogens. After productive (lytic) infection, all human herpesviruses are able to establish life-long latent infection and reactivate... (Review)
Review
Herpesviruses are ubiquitous human pathogens. After productive (lytic) infection, all human herpesviruses are able to establish life-long latent infection and reactivate from it. Latent infection entails suppression of viral replication, maintenance of the viral genome in infected cells, and the ability to reactivate. Most human herpesviruses encode microRNAs (miRNAs) that regulate these processes during latency. Meanwhile, cellular miRNAs are hijacked by herpesviruses to participate in these processes. The viral or cellular miRNAs either directly target viral transcripts or indirectly affect viral infection through host pathways. These findings shed light on the molecular determinants that control the lytic-latent switch and may lead to novel therapeutics targeting latent infection. We discuss the multiple mechanisms by which miRNAs regulate herpesvirus latency, focusing on the patterns in these mechanisms.
Topics: Gene Expression Regulation, Viral; Herpesvirus 8, Human; Humans; Latent Infection; MicroRNAs; Virus Latency; Virus Replication
PubMed: 35746686
DOI: 10.3390/v14061215 -
Archivos de Bronconeumologia Feb 2020
Topics: Humans; Latent Tuberculosis; Mycobacterium tuberculosis
PubMed: 31405608
DOI: 10.1016/j.arbres.2019.07.009 -
Diabetes mellitus and latent tuberculosis infection: an updated meta-analysis and systematic review.BMC Infectious Diseases Nov 2023Previous studies have demonstrated an association between diabetes mellitus (DM) and latent tuberculosis infection (LTBI). This study was conducted to update the current... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have demonstrated an association between diabetes mellitus (DM) and latent tuberculosis infection (LTBI). This study was conducted to update the current understanding of the association between DM and LTBI. By conducting a systematic review and meta-analysis using adjusted odds ratios (aOR) or risk ratios (aRR), we aimed to further explore the association between DM and LTBI and provide essential reference for future research.
METHODS
We conducted comprehensive searches in Embase, Cochrane Library, and PubMed without imposing any start date or language restrictions, up to July 19, 2022. Our study selection encompassed observational research that compared from LTBI positive rates in both DM and non-DM groups and reported aRR or aOR results. The quality of the included studies was assessed utilizing the Newcastle-Ottawa Scale. Pooled effect estimates were calculated using random-effects models, along with their associated 95% confidence intervals (CI).
RESULTS
We included 22 studies involving 68,256 subjects. Three cohort studies were eligible, with a pooled aRR of 1.26 (95% CI: 0.71-2.23). Nineteen cross-sectional studies were eligible, with a pooled aOR of 1.21 (95% CI: 1.14-1.29). The crude RR (cRR) pooled estimate for three cohort studies was 1.62 (95% CI: 1.03-2.57). Among the cross-sectional studies we included, sixteen studies provided crude ORs, and the crude OR (cOR) pooled estimate was 1.64 (95% CI: 1.36-1.97). In the diagnosis of diabetes, the pooled aOR of the HbA1c group was higher than that of self-reported group (pooled aOR: 1.56, 95% CI: 1.24-1.96 vs. 1.17, 95% CI: 1.06-1.28).
CONCLUSION
Our systematic review and meta-analysis suggest a positive association between DM and LTBI. Individuals with DM may have a higher risk of LTBI compared to those without DM. These findings provide important insights for future research and public health interventions in managing LTBI in diabetic populations.
Topics: Humans; Latent Tuberculosis; Cross-Sectional Studies; Diabetes Mellitus; Tuberculin Test; Cohort Studies; Risk Factors; Observational Studies as Topic
PubMed: 37940866
DOI: 10.1186/s12879-023-08775-y -
The Korean Journal of Internal Medicine Mar 2020Management of latent tuberculosis infection (LTBI) is a critical element in the elimination of tuberculosis (TB). However, the low positive predictive value of the... (Review)
Review
Management of latent tuberculosis infection (LTBI) is a critical element in the elimination of tuberculosis (TB). However, the low positive predictive value of the current diagnostic tests and the low acceptance and completion rate of the isoniazid- based regimen are major barriers to the implementation and scale-up of programmatic management of LTBI. In the past decade, there has been some progress in the conception, diagnosis, and treatment of LTBI. LTBI is now understood as a dynamic spectrum rather than the traditional binary distinction between active and latent TB. New insight into LTBI has led to a renewed interest in incipient TB, which would be a potential target for developing new diagnostics and therapeutics of LTBI. Recent studies showed that host transcriptomic signatures could be a potential biomarker for incipient TB. The new shorter rifamycin-based regimens have shown comparable efficacy, but better completion rate and safety compared to the isoniazid-based regimen. In South Korea, LTBI management has been expanded and integrated into key elements of the National Tuberculosis Control Program. For the programmatic approach to LTBI management, the following challenges need to be addressed; target group selection, treatment-related interventions, monitoring and surveillance system, and extending the plan for vulnerable groups.
Topics: Antitubercular Agents; Humans; Isoniazid; Latent Tuberculosis; Republic of Korea; Tuberculosis
PubMed: 32131570
DOI: 10.3904/kjim.2020.029 -
International Journal of Molecular... Dec 2021Latent tuberculosis infection (LTBI) represents a major challenge to curing TB disease. Current guidelines for LTBI management include only three older drugs and their... (Review)
Review
Latent tuberculosis infection (LTBI) represents a major challenge to curing TB disease. Current guidelines for LTBI management include only three older drugs and their combinations-isoniazid and rifamycins (rifampicin and rifapentine). These available control strategies have little impact on latent TB elimination, and new specific therapeutics are urgently needed. In the present mini-review, we highlight some of the alternatives that may potentially be included in LTBI treatment recommendations and a list of early-stage prospective small molecules that act on drug targets specific for latency.
Topics: Drug Therapy, Combination; Humans; Isoniazid; Latent Tuberculosis; Rifampin
PubMed: 34948114
DOI: 10.3390/ijms222413317 -
Clinical Infectious Diseases : An... Mar 2017Despite the well-documented association between diabetes and active tuberculosis, evidence of the association between diabetes and latent tuberculosis infection (LTBI)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite the well-documented association between diabetes and active tuberculosis, evidence of the association between diabetes and latent tuberculosis infection (LTBI) remains limited and inconsistent.
METHODS
We included observational studies that applied either the tuberculin skin test or the interferon gamma release assay for diagnosis of LTBI and that provided adjusted effect estimate for the association between diabetes and LTBI. We searched PubMed and EMBASE through 31 January 2016. The risk of bias of included studies was assessed using a quality assessment tool modified from the Newcastle-Ottawa scale.
RESULTS
Thirteen studies (1 cohort study and 12 cross-sectional studies) were included, involving 38263 participants. The cohort study revealed an increased but nonsignificant risk of LTBI among diabetics (risk ratio, 4.40; 95% confidence interval [CI], 0.50-38.55). For the cross-sectional studies, the pooled odds ratio from the random-effects model was 1.18 (95% CI, 1.06-1.30), with a small statistical heterogeneity across studies (I2, 3.5%). The risk of bias assessment revealed several methodological issues, but the overall direction of biases would reduce the positive causal association between diabetes and LTBI.
CONCLUSIONS
Diabetes was associated with a small but statistically significant risk for LTBI. Findings from this review could be used to inform future cost-effectiveness analysis on the impact of LTBI screening programs among diabetics.
Topics: Cohort Studies; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Humans; Latent Tuberculosis; Odds Ratio; Publication Bias
PubMed: 27986673
DOI: 10.1093/cid/ciw836 -
Frontiers in Cellular and Infection... 2022Human Immunodeficiency virus type 1 (HIV-1) relies on host cell metabolism for all aspects of viral replication. Efficient HIV-1 entry, reverse transcription, and... (Review)
Review
Human Immunodeficiency virus type 1 (HIV-1) relies on host cell metabolism for all aspects of viral replication. Efficient HIV-1 entry, reverse transcription, and integration occurs in activated T cells because HIV-1 proteins co-opt host metabolic pathways to fuel the anabolic requirements of virion production. The HIV-1 viral life cycle is especially dependent on mTOR, which drives signaling and metabolic pathways required for viral entry, replication, and latency. As a central regulator of host cell metabolism, mTOR and its downstream effectors help to regulate the expression of enzymes within the glycolytic and pentose phosphate pathways along with other metabolic pathways regulating amino acid uptake, lipid metabolism, and autophagy. In HIV-1 pathogenesis, mTOR, in addition to HIF-1α and Myc signaling pathways, alter host cell metabolism to create an optimal environment for viral replication. Increased glycolysis and pentose phosphate pathway activity are required in the early stages of the viral life cycle, such as providing sufficient dNTPs for reverse transcription. In later stages, fatty acid synthesis is required for creating cholesterol and membrane lipids required for viral budding. Epigenetics of the provirus fueled by metabolism and mTOR signaling likewise controls active and latent infection. Acetyl-CoA and methyl group abundance, supplied by the TCA cycle and amino acid uptake respectively, may regulate latent infection and reactivation. Thus, understanding and exploring new connections between cellular metabolism and HIV-1 pathogenesis may yield new insights into the latent viral reservoirs and fuel novel treatments and cure strategies.
Topics: Humans; HIV-1; Signal Transduction; Proto-Oncogene Proteins c-myc; TOR Serine-Threonine Kinases; Virus Replication; Latent Infection; Amino Acids
PubMed: 36467738
DOI: 10.3389/fcimb.2022.1068436 -
Drug Discoveries & Therapeutics May 2022Individuals in close contact with multidrug-resistant tuberculosis (MDR-TB) patients are subject to an elevated risk of infection, and may develop latent MDR-TB... (Review)
Review
Individuals in close contact with multidrug-resistant tuberculosis (MDR-TB) patients are subject to an elevated risk of infection, and may develop latent MDR-TB infection. Numerous studies have described latent tuberculosis infection (LTBI) as a reservoir of new TB disease. The screening and treatment of latent MDR-TB infection are challenging. Hereby, we reviewed the epidemiology, current management and prevention approach of LTBI in MDR-TB close contacts, to provide additional information for future research direction and policy design formulation to reduce the LTBI reservoir.
Topics: Humans; Latent Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 35466125
DOI: 10.5582/ddt.2022.01029 -
Clinical Infectious Diseases : An... Nov 2021
Topics: Humans; Latent Tuberculosis; Tuberculin Test; Tuberculosis; United States
PubMed: 32588882
DOI: 10.1093/cid/ciaa850