-
Journal of Clinical Virology : the... Jun 2024Epstein-Barr virus (EBV) is a ubiquitous and oncogenic virus that is associated with various malignancies and non-malignant diseases and EBV DNA detection is widely used...
Epstein-Barr virus (EBV) is a ubiquitous and oncogenic virus that is associated with various malignancies and non-malignant diseases and EBV DNA detection is widely used for the diagnosis and prognosis prediction for these diseases. The dried blood spots (DBS) sampling method holds great potential as an alternative to venous blood samples in geographically remote areas, for individuals with disabilities, or for newborn blood collection. Therefore, the objective of this study was to assess the viability of detecting EBV DNA load from DBS. Matched whole blood and DBS samples were collected for EBV DNA extraction and quantification detection. EBV DNA detection in DBS presented a specificity of 100 %. At different EBV DNA viral load in whole blood, the sensitivity of EBV DNA detection in DBS was 38.78 % (≥1 copies/mL), 43.18 % (≥500 copies/mL), 58.63 % (≥1000 copies/mL), 71.43 % (≥2000 copies/mL), 82.35 % (≥4000 copies/mL), and 92.86 % (≥5000 copies/mL), respectively. These results indicated that the sensitivity of EBV DNA detection in DBS increased with elevating viral load. Moreover, there was good correlation between EBV DNA levels measured in whole blood and DBS, and on average, the viral load measured in whole blood was about 6-fold higher than in DBS. Our research firstly demonstrated the feasibility of using DBS for qualitative and semi-quantitative detection of EBV DNA for diagnosis and surveillance of EBV-related diseases.
PubMed: 38954911
DOI: 10.1016/j.jcv.2024.105710 -
Journal of the National Cancer Institute Jul 2024Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV (PWH) and solid organ transplant...
BACKGROUND
Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV (PWH) and solid organ transplant recipients (SOTRs), two immunosuppressed populations, may help identify novel etiologic relationships with infectious agents.
METHODS
We utilized two linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified based on site and histology codes. Standardized incidence ratios (SIRs) were used to compare risk in PWH and SOTRs with the general population. For selected cancer entities, incidence rate ratios (IRRs) were calculated for indicators of immunosuppression within each population.
FINDINGS
We identified 38,047 cancer cases in SOTRs and 53,592 in PWH, yielding overall SIRs of 1.66 (95%CI = 1.65-1.68) and 1.49 (95%CI = 1.47-1.50), respectively. Forty-three cancer entities met selection criteria, including conjunctival squamous cell carcinoma (SCC) (PWH SIR = 7.1, 95%CI = 5.5-9.2; SOTRs SIR = 9.4; 95%CI = 6.8-12.6). Sebaceous adenocarcinoma was elevated in SOTRs (SIR = 16.2; 95%CI = 14.0-18.6) and, among SOTRs, associated with greater risk in lung/heart transplant recipients compared to recipients of other organs (IRR = 2.3; 95%CI = 1.7-3.2). Salivary gland tumors, malignant fibrous histiocytoma (MFH), and intrahepatic cholangiocarcinoma showed elevated risk in SOTRs (SIR = 3.9; SIR = 4.7; and SIR = 3.2, respectively) but not in PWH. However, risks for these cancers were elevated following an AIDS diagnosis among PWH (IRR = 2.4; IRR = 4.3; and IRR = 2.0, respectively).
INTERPRETATION
Elevated SIRs among SOTRs and PWH, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival SCC, sebaceous adenocarcinoma, salivary gland tumors, MFH, and intrahepatic cholangiocarcinoma.
PubMed: 38954841
DOI: 10.1093/jnci/djae159 -
ACS Chemical Biology Jul 2024Hepatitis C virus (HCV) is a positive-stranded RNA virus that mainly causes chronic hepatitis, cirrhosis and hepatocellular carcinoma. Recently we confirmed m5C...
Hepatitis C virus (HCV) is a positive-stranded RNA virus that mainly causes chronic hepatitis, cirrhosis and hepatocellular carcinoma. Recently we confirmed m5C modifications within NS5A gene of HCV RNA genome. However, the roles of the m5C modification and its interaction with host proteins in regulating HCV's life cycle, remain unexplored. Here, we demonstrate that HCV infection enhances the expression of the host m5C reader YBX1 through the transcription factor MAX. YBX1 acts as an m5C reader, recognizing the m5C-modified NS5A C7525 site in the HCV RNA genome and significantly enhancing HCV RNA stability. This m5C-modification is also required for YBX1 colocalization with lipid droplets and HCV Core protein. Moreover, YBX1 facilitates HCV RNA replication, as well as viral assembly/budding. The tryptophan residue at position 65 (W65) of YBX1 is critical for these functions. Knockout of YBX1 or the application of YBX1 inhibitor SU056 suppresses HCV RNA replication and viral protein translation. To our knowledge, this is the first report demonstrating that the interaction between host m5C reader YBX1 and HCV RNA m5C methylation facilitates viral replication. Therefore, hepatic-YBX1 knockdown holds promise as a potential host-directed strategy for HCV therapy.
PubMed: 38954741
DOI: 10.1021/acschembio.4c00322 -
A mathematical model of COVID-19 with multiple variants of the virus under optimal control in Ghana.PloS One 2024In this paper, we suggest a mathematical model of COVID-19 with multiple variants of the virus under optimal control. Mathematical modeling has been used to gain deeper...
In this paper, we suggest a mathematical model of COVID-19 with multiple variants of the virus under optimal control. Mathematical modeling has been used to gain deeper insights into the transmission of COVID-19, and various prevention and control strategies have been implemented to mitigate its spread. Our model is a SEIR-based model for multi-strains of COVID-19 with 7 compartments. We also consider the circulatory structure to account for the termination of immunity for COVID-19. The model is established in terms of the positivity and boundedness of the solution and the existence of equilibrium points, and the local stability of the solution. As a result of fitting data of COVID-19 in Ghana to the model, the basic reproduction number of the original virus and Delta variant was estimated to be 1.9396, and the basic reproduction number of the Omicron variant was estimated to be 3.4905, which is 1.8 times larger than that. We observe that even small differences in the incubation and recovery periods of two strains with the same initial transmission rate resulted in large differences in the number of infected individuals. In the case of COVID-19, infections caused by the Omicron variant occur 1.5 to 10 times more than those caused by the original virus. In terms of the optimal control strategy, we formulate three control strategies focusing on social distancing, vaccination, and testing-treatment. We have developed an optimal control model for the three strategies outlined above for the multi-strain model using the Pontryagin's Maximum Principle. Through numerical simulations, we analyze three optimal control strategies for each strain and also consider combinations of the two control strategies. As a result of the simulation, all control strategies are effective in reducing disease spread, in particular, vaccination strategies are more effective than the other two control strategies. In addition the combination of the two strategies also reduces the number of infected individuals by 1/10 compared to implementing one strategy, even when mild levels are implemented. Finally, we show that if the testing-treatment strategy is not properly implemented, the number of asymptomatic and unidentified infections may surge. These results could help guide the level of government intervention and prevention strategy formulation.
Topics: COVID-19; Humans; Ghana; SARS-CoV-2; Basic Reproduction Number; Models, Theoretical
PubMed: 38954691
DOI: 10.1371/journal.pone.0303791 -
PloS One 2024In Europe, two fastidious phloem-limited pathogens, 'Candidatus Phytoplasma solani' (16SrXII-A) and 'Candidatus Arsenophonus phytopathogenicus', are associated with...
In Europe, two fastidious phloem-limited pathogens, 'Candidatus Phytoplasma solani' (16SrXII-A) and 'Candidatus Arsenophonus phytopathogenicus', are associated with rubbery taproot disease (RTD) and syndrome basses richesses (SBR) of sugar beet, respectively. Both diseases can significantly reduce yield, especially when accompanied by root rot fungi. This study investigates the presence, geographic distribution and genetic traits of fastidious pathogens and the accompanying fungus, Macrophomina phaseolina, found on sugar beet across four geographically separated plains spanning seven countries in Central Europe. The survey revealed variable incidences of symptoms linked to these fastidious pathogens in the Pannonian and Wallachian Plains, sporadic occurrence in the North European Plain, and no symptomatic sugar beet in the Bohemian Plain. Molecular analyses unveiled the occurrence of both 'Ca. P. solani' and 'Ca. A. phytopathogenicus' throughout Central Europe, with a predominance of the phytoplasma. These fastidious pathogens were detected in all six countries surveyed within the Pannonian and Wallachian Plains, with only a limited presence of various phytoplasmas was found in the North European Plain, while no fastidious pathogens were detected in Bohemia, aligning with observed symptoms. While 16S rDNA sequences of 'Ca. P. solani' remained highly conserved, multi-locus characterization of two more variable loci (tuf and stamp) unveiled distinct variability patterns across the plains. Notably, the surprising lack of variability of tuf and stamp loci within Central Europe, particularly the Pannonian Plain, contrasted their high variability in Eastern and Western Europe, corresponding to epidemic and sporadic occurrence, respectively. The current study provides valuable insights into the genetic dynamics of 'Ca. P. solani' in Central Europe, and novel findings of the presence of 'Ca. A. phytopathogenicus' in five countries (Slovakia, Czech Republic, Austria, Serbia, and Romania) and M. phaseolina in sugar beet in Slovakia. These findings emphasize the need for further investigation of vector-pathogen(s)-plant host interactions and ecological drivers of disease outbreaks.
Topics: Beta vulgaris; Europe; Plant Diseases; Phytoplasma; Phloem; Phylogeny; Ascomycota; Geography; Prevalence
PubMed: 38954690
DOI: 10.1371/journal.pone.0306136 -
Annual Review of Virology Jul 2024The nucleoplasm, the cytosol, the inside of virions, and again the cytosol comprise the world in which the capsids of alphaherpesviruses encounter viral and host... (Review)
Review
The nucleoplasm, the cytosol, the inside of virions, and again the cytosol comprise the world in which the capsids of alphaherpesviruses encounter viral and host proteins that support or limit them in performing their tasks. Here, we review the fascinating conundrum of how specific protein-protein interactions late in alphaherpesvirus infection orchestrate capsid nuclear assembly, nuclear egress, and cytoplasmic envelopment, but target incoming capsids to the nuclear pores in naive cells to inject the viral genomes into the nucleoplasm for viral transcription and replication. Multiple capsid interactions with viral and host proteins have been characterized using viral mutants and assays that reconstitute key stages of the infection cycle. Keratinocytes, fibroblasts, mucosal epithelial cells, neurons, and immune cells employ cell type-specific intrinsic and cytokine-induced resistance mechanisms to restrict several stages of the viral infection cycle. However, concomitantly, alphaherpesviruses have evolved countermeasures to ensure efficient capsid function during infection.
PubMed: 38954634
DOI: 10.1146/annurev-virology-100422-022751 -
The Journal of Clinical Investigation Jul 2024Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in immunocompromised individuals such as kidney transplant recipients (KTRs). The...
Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in immunocompromised individuals such as kidney transplant recipients (KTRs). The exact mechanisms underlying the disability of cytotoxic T cells to provide sufficient protection against CMV in immunosuppressed individuals have not been identified yet. Here, we performed in-depth metabolic profiling of CMV-specific CD8+ T cells in immunocompromised patients and show the development of metabolic dysregulation at the transcriptional, protein, and functional level of CMV-specific CD8+ T cells in KTRs with non-controlled CMV infection. These dysregulations comprise impaired glycolysis and increased mitochondrial stress, which is associated with an intensified expression of the nicotinamide adenine dinucleotide nucleotidase (NADase) CD38. Inhibiting NADase activity of CD38 reinvigorated the metabolism and improved cytokine production of CMV-specific CD8+ T cells. These findings were corroborated in a mouse model of CMV infection under conditions of immunosuppression. Thus, dysregulated metabolic states of CD8+ T cells could be targeted by inhibiting CD38 to reverse hypo-responsiveness in individuals who fail to control chronic viral infection.
PubMed: 38954588
DOI: 10.1172/JCI179561 -
Natural Product Research Jul 2024The ocean's vast and diverse ecosystem offers a rich reservoir of bioactive compounds with immense clinical potential. Marine organisms produce structurally unique and...
The ocean's vast and diverse ecosystem offers a rich reservoir of bioactive compounds with immense clinical potential. Marine organisms produce structurally unique and biologically active compounds, leading to breakthroughs in therapeutic development. Notable examples include anticancer agents like trabectedin and cytarabine, and the analgesic ziconotide. Marine compounds also exhibit potent antimicrobial and antiviral properties, addressing critical challenges like antibiotic resistance and emerging viral infections. Despite the promise, challenges such as sustainable harvesting and complex extraction processes persist. Advances in synthetic biology and metabolic engineering provide solutions for sustainable production, ensuring a stable supply of these valuable compounds. The integration of marine bioactives into modern medicine could revolutionize treatments for cancer, chronic pain, and infectious diseases, underscoring the need for continued investment in marine bioprospecting and biotechnological innovation.
PubMed: 38954510
DOI: 10.1080/14786419.2024.2373965 -
Journal of Hunger & Environmental... 2024We examined associations between adolescent self-reported hunger, health risk behaviors, and adverse experiences during the 2018-2019 school year. Youth Risk Behavior...
We examined associations between adolescent self-reported hunger, health risk behaviors, and adverse experiences during the 2018-2019 school year. Youth Risk Behavior Survey data were pooled from 10 states. Prevalence ratios were calculated, and we assessed effect measure modification by sex. The prevalence of self-reported hunger was 13%. Self-reported hunger was associated with a higher prevalence of every health risk behavior/adverse experience analyzed, even after adjusting for sex, grade, and race/ethnicity. Sex did not modify associations. Findings underscore needs for longitudinal research with more robust measures of adolescent food insecurity to clarify the temporality of relationships.
PubMed: 38954493
DOI: 10.1080/19320248.2022.2088263 -
JCI Insight Jul 2024Upon infection, naïve CD8+ T cells differentiate into cytotoxic effector cells to eliminate the pathogen-infected cells. Although many mechanisms underlying this...
Upon infection, naïve CD8+ T cells differentiate into cytotoxic effector cells to eliminate the pathogen-infected cells. Although many mechanisms underlying this process have been demonstrated, the regulatory role of chromatin remodel system in this process remains largely unknown. Here we showed that BRD7, a component of the polybromo-associated BRG1-associated factor complex (PBAF), was required for naïve CD8+ T cells to differentiate into functional short-lived effector cells (SLECs) in response to acute infections caused by influenza virus or lymphocytic choriomeningitis virus (LCMV). BRD7-deficiency in CD8+ T cells resulted in profound defects in effector population and functions, thereby impairing viral clearance and host recovery. Further mechanical studies indicated that the expression of BRD7 significantly turned to high from naïve CD8+ T cells to effector cells, bridged BRG1 and PBRM1 to the core module of PBAF complex, consequently facilitating the assembly of PBAF complex rather than BAF complex in the effector cells. The PBAF complex changed the chromatin accessibility at the loci of Tbx21 gene and up-regulated its expression, leading to the maturation of effector T cells. Our research confirms BRD7 and the PBAF complex are key in CD8+ T cell development and present a significant target for advancing immune therapies.
PubMed: 38954484
DOI: 10.1172/jci.insight.171605