Virus Reactivation Research Articles

Successful Management of Progressive Multifocal Leukoencephalopathy in an HIV/AIDS Patient: A Therapeutic Case Report

Background: Progressive multifocal leukoencephalopathy (PML), a rare and devastating opportunistic infection caused by JC virus reactivation, typically carries a poor prognosis in immunocompromised individuals, particularly those with HIV. Aim: To report a remarkable case of full recovery in an HIV-positive patient with PML and highlight the significance of prompt recognition, diagnosis, and combination antiretroviral therapy (cART). Case Summary: A 34-year-old HIV-positive male presented with progressive disturbances of consciousness and movement. MRI revealed multifocal white matter lesions, and JC virus DNA was detected in cerebrospinal fluid. Despite initial deterioration, the patient achieved full recovery with cART. Conclusion: This exceptional outcome emphasizes the critical importance of vigilant monitoring, prompt diagnosis, and effective management strategies for PML in HIV patients, highlighting the potential for full recovery with optimal cART.

Epstein-Barr virus reactivation in pediatric allogeneic stem cell transplant recipients: an 11-year experience on viral load and B lymphocyte monitoring strategy.

Epstein-Barr virus (EBV) reactivation represents a frequent condition after allogeneic hematopoietic stem cell transplantation (allo-HCT) and can cause the development of a severe complication: post-transplant lymphoproliferative disease (PTLD). This retrospective study aims at investigating the incidence of EBV reactivations and analyzing the potential impact of recipient/donor-related transplant-related factors in pediatric patients. The secondary objective was to study the consequences of the approach used at our center regarding the initiation of pre-emptive therapy. This study used a retrospective evaluation of patients aged ≤25 years who received an allo-HCT at IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Giannina Gaslini, between 2012 and 2022, with follow-up censored in July 2023. Criteria to start rituximab were as follows: a viral load ≥20,000 copies/105 PBMCs or ≥10,000/105 PBMCs associated with a rise in the proportion of CD 20+ lymphocytes. Overall, 214 allo-HCTs were performed in 189 patients. A total of 127 (59.3%) procedures were complicated by at least one EBV reactivation, but in only one rituximab was administered. All other reactivations were characterized by viremia below reference ranges and no increase in CD20+ lymphocytes, without clinical consequences. Risk factors for EBV reactivation identified were associated with delayed immune reconstitution. These results could suggest the effectiveness of the approach used in providing pre-emptive therapy. The strategy adopted differs from that highlighted by other studies and allowed the reduction of the number of children who received rituximab. It has proven effective considering the low incidence rate of PTLD and reduces the risk of rituximab-related adverse events.

Immunogenicity and Safety of the Recombinant Adjuvanted Herpes Zoster Vaccine in Patients with Chronic Lymphocytic Leukemia and Multiple Myeloma

Background/objectives: Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are susceptible to viral infections, including varicella-zoster virus (VZV) reactivation due to both disease-related and treatment-induced immunosuppression. The recombinant adjuvanted herpes zoster vaccine (RZV) has shown high efficacy in immunocompetent adults, but immunogenicity data in CLL and MM patients are limited. This study evaluates the immunogenicity and safety of RZV in this population. Methods: Patients with CLL and MM vaccinated with RZV (administered in two doses at least one month apart) were included in the study. Pre- and post-vaccination anti-VZV IgM and IgG antibody levels were measured to assess immunogenicity, and adverse events (AEs) were captured for safety evaluation. Results: Seventy-eight patients received both vaccine doses, and 71 had post-vaccination samples. Most of the patients were IgM seronegative and IgG seropositive before vaccination. Pre-vaccination IgG levels were higher in CLL patients compared to MM patients (p = 0.001), while post-vaccination IgG levels significantly increased in both CLL (p < 0.0001) and MM (p < 0.0001) patients. In actively treated CLL patients, pre-vaccination IgG levels were significantly lower than in not actively treated patients (p = 0.002). Post-vaccination IgG levels were lower in MM patients receiving antiviral prophylaxis concurrently with the vaccination (p = 0.013). AEs were reported in 49.4% of patients after the first dose and 48.7% after the second dose, mostly mild (local or low-grade systemic). One case of immune thrombocytopenia was noted. Conclusions: RZV demonstrated strong immunogenicity and acceptable safety in CLL and MM patients, significantly boosting IgG levels, even in actively treated or heavily pretreated patients.

Monitoring Immune Dysfunction in Critically Ill Patients with Carbapenem-Resistant Acinetobacter baumannii Sepsis Treated with Regimens Including Cefiderocol: A Pilot Study to Identify Accessible Biomarkers to Stratify Patients’ Prognosis

Background: Multidrug-resistant Acinetobacter baumannii (CRAB) infections are a serious problem in critical care. This study aims to develop an early prognostic score for immune paralysis, using practical and cost-effective parameters, to predict ICU mortality in patients with CRAB infections being treated with Cefiderocol. Methods: We carried out an observational pilot study on consecutive patients hospitalized in the ICU with ensuing septic Acinetobacter baumannii infections treated with Cefiderocol monotherapy or Cefiderocol including combinations. We investigated the predictive power of lymphocyte counts, lymphocyte subpopulations, serum cholinesterase levels, and reactivation of herpes viruses. Results: Overall, 36 of 39 patients entered in our analysis: 20 survivors and 16 deceased. A total of 12 patients developed bacteremia, 19 patients had HAP/VAP, and 5 patients had a soft tissue infection. Univariate analyses of factors associated with unfavorable outcome revealed a significant association for age (OR: 1.5, CI: 1.11–2.02), SAPS II (OR: 1.05, CI: 1.01–1.1), SOFA score (OR: 1.37, CI: 1.06–1.76), lymphocytopenia (OR: 32.5, CI: 3.45–306.4), viral reactivation (OR: 9.75, CI: 1.72–55.4), and cholinesterase drop <1600 U/L (OR: 39.7, CI: 5.8–271.6). At variance, monotherapy or associations with Cefiderocol were not associated. In the final multivariable model, the only independent predictors of death were age (OR: 1.42, CI: 0.98–2.05), lymphocytopenia (OR: 18.2, CI: 0.87–371), and cholinesterase drop to below 1600 U/L (OR: 9.7, CI: 0.77–123.7). Conclusions: Age, lymphocytopenia, and serum cholinesterase drops, which were nearly significantly associated with an unfavorable outcome, may help pinpoint patients with acute immune paralysis during sepsis. Knowledge of such an immune state may in turn directly influence patients’ care.

Identifying the amino acid domains of ORF59 responsible for interactions with ORF57 and PAN RNA during KSHV lytic replication.

Kaposi's sarcoma-associated herpesvirus (KSHV) DNA polymerase processivity factor, ORF59, is a lytic protein essential for viral DNA synthesis as part of the core replication complex. The multifunctional nature of ORF59 has prompted the investigation into its various functional domains. Prior studies of ORF59 have identified dimerization, DNA interaction, and polymerase interaction domains. The regions of ORF59 responsible for the interaction with the viral mRNA transport accumulation protein (MTA/ORF57) and the viral long non-coding polyadenylated nuclear (PAN) RNA have not been explored. Using a series of previously characterized ORF59 deletion KSHV BACmid mutants, we identified the domains of ORF59 that interact with ORF57 and PAN RNA. Interestingly, amino acids 51-100 were essential for interacting with both ORF57 and PAN RNA. Using this information, we generated a plasmid that expresses a DsRed-tagged polypeptide spanning amino acids 30-100 of ORF59. When the 30-100 aa DsRed-tagged polypeptide expression plasmid was transfected into KSHV wild-type iSLK cells prior to lytic reactivation, a dominant-negative inhibition of virus replication was observed, resulting in a decrease of infectious virus production. Our data suggest that interactions between ORF59 with ORF57 and PAN RNA are important to successful lytic replication.IMPORTANCETo better understand the Kaposi's sarcoma-associated herpesvirus (KSHV) DNA polymerase processivity factor ORF59, we investigated the interaction of ORF59 with ORF57 and polyadenylated nuclear (PAN) RNA. We used a previously characterized KSHV BACmid containing internal deletions of ORF59 to identify the domains of ORF59 that interact with ORF57 and PAN RNA. Our study revealed multiple domains of ORF59 that are essential for its association with PAN RNA. These domains span amino acids 51-100, 251-300, and 351-396. Additional experiments confirmed amino acids 51-100 are critical for the interaction between ORF59 and ORF57. Using this information, we generated an expression plasmid encompassing the ORF57 and PAN RNA interaction domains of ORF59. The ORF59 polypeptide expression plasmid of amino acids 30-100 functioned as a dominant negative inhibitor during viral reactivation and caused a decrease in virus production. These findings provide valuable insights into the key domains of ORF59, essential for its functionality, and ultimately the production of infectious viruses.

A Survey on Knowledge and Attitudes Towards Vaccination Against Herpes Zoster Virus Among Medical Oncologists for Patients with Solid Tumors.

Herpes zoster (HZ) virus reactivation is a significant medical problem among immunocompromised patients, especially considering its potential complications. Although the recombinant HZ vaccine has demonstrated > 90% efficacy against HZ in adults, its use is not as frequent as needed in daily oncology practice due to several barriers, including oncologists' knowledge, patients' willingness, and organizational issues. A web-based survey was sent to 139 oncologists treating solid tumors concerning their knowledge and attitudes toward the adjuvanted gE-based recombinant HZ vaccination. The survey included questions regarding the characteristics of medical oncologists participating, such as the type of hospital, main field of expertise, percent of work with patients, awareness of the HZ risk in cancer patients, knowledge of scientific data and scientific societies guidelines on HZ vaccination, familiarity with vaccinations, frequency of HZ detection in clinical practice, barriers, and challenges toward vaccine administration. Fifty-four physicians (46%; 95% CI 0.2918 to 0.5069) responded to all the questions. The main reason for non-response was the lack of time due to the overwhelming burden of assistance. When the survey was launched, 31 participants reported good knowledge of scientific and clinical data of HZ vaccines, 10% none, and 36 were aware of guidelines. Reported barriers included knowledge of the problem, patients' willingness, and organizational issues. Surveying medical oncologists on the adjuvanted gE-based recombinant HZ vaccination provides essential insights into their knowledge, attitudes, and practices regarding vaccination for cancer patients. These data suggest that continuing medical education is necessary to implement HZ vaccination prescription among oncologists.

Kaposi Sarcoma as a Possible Cutaneous Adverse Effect of ChAdOx1 nCov-19 Vaccine: A Case Report

The COVID-19 pandemic prompted the rapid development of vaccines, including the ChAdOx1 nCov-19 (AstraZeneca) vaccine. While effective, adverse effects have been reported, including cutaneous manifestations. Kaposi sarcoma (KS), a vascular tumor linked to Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV-8), has seen increased detection during the pandemic. This study reports a case of classic cutaneous KS in a 79-year-old male following the first dose of the ChAdOx1 nCov-19 vaccine, without prior SARS-CoV-2 infection. The patient developed multiple reddish-blue papules on his legs and feet, confirmed as KS through histopathology. Treatment included radiotherapy and sequential chemotherapy with Doxorubicin. The potential reactivation of latent HHV-8 by the vaccine is explored through mechanisms involving the SARS-CoV-2 spike protein and adenovirus vector, which may induce immune responses and inflammatory pathways. Although establishing a direct causal link remains challenging, the case highlights the need for vigilance regarding KS reactivation post-vaccination. Further large-scale studies are warranted to elucidate the relationship between COVID-19 vaccines and latent virus reactivation, ensuring comprehensive safety assessments and informed public health decisions.

Risk of Hepatitis B Virus Reactivation in COVID-19 Patients Receiving Immunosuppressive Treatment: A Prospective Study.

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed HBV screening on all Romanian adults hospitalized in four COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment, or baseline immunosuppressive conditions, and we conducted a virological follow-up on these patients at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed for 13 patients with positive hepatitis B surface antigen (HBsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with a de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) for all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish appropriate and cost-effective management for these patients.

Epstein-Barr virus as a potentiator of autoimmune diseases.

The Epstein-Barr virus (EBV) is epidemiologically associated with development of autoimmune diseases, including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis and multiple sclerosis. Although there is well-established evidence for this association, the underlying mechanistic basis remains incompletely defined. In this Review, we discuss the role of EBV infection as a potentiator of autoimmune rheumatic diseases. We review the EBV life cycle, viral transcription programmes, serological profiles and lytic reactivation. We discuss the epidemiological and mechanistic associations of EBV with systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis and multiple sclerosis. We describe the potential mechanisms by which EBV might promote autoimmunity, including EBV nuclear antigen 1-mediated molecular mimicry of human autoantigens; EBV-mediated B cell reprogramming, including EBV nuclear antigen 2-mediated dysregulation of autoimmune susceptibility genes; EBV and host genetic factors, including the potential for autoimmunity-promoting strains of EBV; EBV immune evasion and insufficient host responses to control infection; lytic reactivation; and other mechanisms. Finally, we discuss the therapeutic implications and potential therapeutic approaches to targeting EBV for the treatment of autoimmune disease.

Emerging small-molecule antiviral agents in long COVID prevention.

Long COVID, or Post-Acute Sequelae of COVID-19 (PASC), was characterized by persistent symptoms such as fatigue, shortness of breath, and cognitive impairments. These symptoms, emerging one to 2months post-infection and persisting for several months, cannot be attributed to other diagnoses. The pathophysiology of long COVID remained elusive; however, emerging studies suggested multiple potential mechanisms, including the reactivation of Epstein-Barr virus, persistent SARS-CoV-2 reservoirs, neuroinflammation, and vascular damage, which may contribute to its development. Long COVID affected multiple organ systems, including respiratory, circulatory, and nervous systems, leading to a range of functional impairments. Additionally, it showed a profound impact on mental health, manifesting as anxiety and depression, which significantly degraded the quality of life. The absence of definitive treatments underscored the importance of prevention. Recent evidence indicated that early antiviral intervention-particularly with small-molecule drugs such as Metformin, Ensitrelvir, Molnupiravir, and Nirmatrelvir-may effectively reduce the incidence of long COVID. This underscored the promising role of small-molecule compounds in mitigating long-term COVID-19 consequences, offering a novel preventive strategy against long COVID and its extensive impacts on patients.

A fur plucking model to study herpes simplex virus reactivation and recurrent disease.

Herpes simplex viruses (HSV-1 and HSV-2) have infected over half of the US adult population to cause a lifelong, persistent infection; however, our understanding of the mechanisms that govern HSV reactivation and recurrent disease is incomplete. This is in part due to limitations in the animal models used to study recurrent disease, which are laborious and inefficient in mice. To address this technical gap, we developed a mouse model in which fur plucking after flank skin infection is sufficient to induce episodes of HSV reactivation and recurrent disease. Our work provides a model for the field to investigate the pathogenic mechanisms of HSV and immune responses during recurrent disease and provides an opportunity to investigate the neurobiology of HSV infection.

An updated approach to the evaluation of the urinary sediment.

Examination of the urinary sediment (U-sed) is an important non-invasive, rapid, and inexpensive tool for the diagnosis and surveillance over time of renal diseases. In this Educational Review, we describe first how to collect, prepare, and examine urine samples in order to obtain reliable results. Then, we describe the U-sed findings in isolated microscopic hematuria, glomerular diseases, acute interstitial nephritis, acute kidney injury, reactivation of the BK virus in kidney transplant recipients, and crystalluric genetic diseases.

Role of SARS-CoV-2-specific memory B cells promoting immune protection after booster vaccination in solid organ transplantation.

Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear. We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination. We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion. Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients.

5164 Long COVID patients with menstrual symptoms: a retrospective study in Japan

Abstract Disclosure: F. Otsuka: None. Y. Sakurada: None. Y. Matsuda: None. T. Hasegawa: None. Y. Otsuka: None. Y. Nakano: None. K. Tokumasu: None. K. Yamamoto: None. N. Sunada: None. H. Honda: None. H. Hagiya: None. K. Ueda: None. It has been recognized that about one third of patients may suffer from prolonged illness after surviving from the acute phase of COVID-19. Various symptoms of the prolonged illness have been evaluated by many institutions including WHO. However, the mechanisms of the prolonged symptoms have yet to be elucidated. Long COVID is a complicated illness that develops after SARS-CoV-2 infection, independent of the severity of COVID-19. Long COVID is defined as symptoms that occur within 3 months after the initial infection and persist for at least 2 months. The major symptoms of long COVID include general fatigue, post-exertional malaise, headache, insomnia, dyspnea, cognitive dysfunction, low-grade fever, and muscle pain. Proposed pathophysiological mechanisms of long COVID include pathogen persistence and viral reactivation, immune dysregulation and autoimmunity, neurological abnormalities, tissue damage due to hypoperfusion and/or microclots, autonomic and endocrine dysfunctions, and dysregulation of microbiomes. In the present study, we aimed to elucidate the impact of long COVID on female reproductive health. In this retrospective study, medical records of patients who visited our long COVID clinic and clinical trends of their menstrual symptoms were evaluated. In our study, of 349 female patients who visited our clinic between Feb 2021 and Mar 2023, 223 patients with long COVID (18-50 years) were included. It was revealed that 44 females (19.7%) had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were significantly older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity (63.6%) was the most frequent menstrual symptom, followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications with menstrual complaints. Scores indicating fatigue and QOL were significantly worse in long COVID patients with menstrual symptoms. Endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints although plasma adrenocorticotropin levels were not altered. Hence, long COVID has an impact on women’s reproductive and mental health. Presentation: 6/1/2024

5164 Long COVID patients with menstrual symptoms: a retrospective study in Japan

Abstract Disclosure: F. Otsuka: None. Y. Sakurada: None. Y. Matsuda: None. T. Hasegawa: None. Y. Otsuka: None. Y. Nakano: None. K. Tokumasu: None. K. Yamamoto: None. N. Sunada: None. H. Honda: None. H. Hagiya: None. K. Ueda: None. It has been recognized that about one third of patients may suffer from prolonged illness after surviving from the acute phase of COVID-19. Various symptoms of the prolonged illness have been evaluated by many institutions including WHO. However, the mechanisms of the prolonged symptoms have yet to be elucidated. Long COVID is a complicated illness that develops after SARS-CoV-2 infection, independent of the severity of COVID-19. Long COVID is defined as symptoms that occur within 3 months after the initial infection and persist for at least 2 months. The major symptoms of long COVID include general fatigue, post-exertional malaise, headache, insomnia, dyspnea, cognitive dysfunction, low-grade fever, and muscle pain. Proposed pathophysiological mechanisms of long COVID include pathogen persistence and viral reactivation, immune dysregulation and autoimmunity, neurological abnormalities, tissue damage due to hypoperfusion and/or microclots, autonomic and endocrine dysfunctions, and dysregulation of microbiomes. In the present study, we aimed to elucidate the impact of long COVID on female reproductive health. In this retrospective study, medical records of patients who visited our long COVID clinic and clinical trends of their menstrual symptoms were evaluated. In our study, of 349 female patients who visited our clinic between Feb 2021 and Mar 2023, 223 patients with long COVID (18-50 years) were included. It was revealed that 44 females (19.7%) had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were significantly older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity (63.6%) was the most frequent menstrual symptom, followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications with menstrual complaints. Scores indicating fatigue and QOL were significantly worse in long COVID patients with menstrual symptoms. Endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints although plasma adrenocorticotropin levels were not altered. Hence, long COVID has an impact on women’s reproductive and mental health. Presentation: 6/1/2024

Evaluation of new-onset BK viruria in post-renal transplant recipients by quantitative PCR

BackgroundThe BK polyomavirus infection poses a substantial challenge for organ transplant recipients due to immunosuppression, resulting in BK virus-associated nephropathy (BKVAN) and a considerable risk of graft loss. Screening and prompt decrease of immunosuppression are essential for averting these consequences. We examined the frequency of BK viruria (viral load in urine) among post-renal transplant recipients, along with its association with age, viral load, and the timing of viral reactivation. MethodsThe prospective cohort study was conducted at the Tertiary Care Hospital in Rawalpindi over a 12-month period, from January 1 to December 31, 2023. Urine specimens from 108 renal transplant recipients were collected and analysed for BK viruria every three months during the follow-up assessments. DNA extraction was performed using TANbead extractor, and amplification was carried out with Bio-Rad CFX-96 thermal cycler using Sacace TM amplification kit. Data was analysed using SPSS version 27. ResultsIn the cohort of 108 renal transplant recipients, BK viruria was detected in 16.7 % of cases. There was a higher prevalence of BK viruria in females (20 %) than males (16 %). The majority of positive cases were within the 41–60 years age group (61.1 %). Most of the patients (66.6 %) had viral loads below 1 million copies/ml. BK viruria was predominantly detected during the third quarter (between 7 and 9 months) post-transplant. The Chi-square test was applied between age and viral load, showing a significant association (p = 0.01). Similarly, gender and viral load also showed a significant relationship (p = 0.019). ConclusionThe study showed the frequency of 16.7 % of BK viruria in our small cohort after renal transplantation during the initial 12 months post-transplant. Age of recipients correlated with viral load and time of viral reactivation: middle-aged recipients had higher viral loads. BK viruria increased progressively over the initial nine months, with peak incidence in the third quarter post-transplant.

Orthogonal Persulfide Generation through Precision Tools Provides Insights into Mitochondrial Sulfane Sulfur.

The sulfane sulfur pool, comprised of persulfide (RS-SH) and polysulfide (RS-SnH) derived from hydrogen sulfide (H2S), has emerged as a major player in redox biochemistry. Mitochondria, besides energy generation, serve as significant cellular redox hubs, mediate stress response and cellular health. However, the effects of endogenous mitochondrial sulfane sulfur (MSS) remain largely uncharacterized as compared with their cytosolic counterparts, cytosolic sulfane sulfur (CSS). To investigate this, we designed a novel artificial substrate for mitochondrial 3-mercaptopyruvate sulfurtransferase (3-MST), a key enzyme involved in MSS biosynthesis. Using cells expressing a mitochondrion-localized persulfide biosensor, we demonstrate this tool's ability to selectively enhance MSS. While H2S was previously known to suppress human immunodeficiency virus (HIV-1), we found that MSS profoundly affected the HIV-1 life cycle, mediating viral reactivation from latency. Additionally, we provide evidence for the role of the host's mitochondrial redox state, membrane potential, apoptosis, and respiration rates in managing HIV-1 latency and reactivation. Together, dynamic fluctuations in the MSS pool have a significant and possibly conflicting effect on HIV-1 viral latency. The precision tools developed herein allow for orthogonal generation of persulfide within both mitochondria and the cytosol and will be useful in interrogating disease biology.

Hepatitis B and/or C virus reactivation in patients receiving chemotherapy: An observational study

Background: Viral hepatitis reactivation occurs during various chemotherapy treatments. Patients with high serum titer levels of Hepatitis B virus (HBV) DNA before chemotherapy and those receiving intensive chemotherapy for hematological malignancies are particularly at risk. Aims and Objectives: This study aimed to determine the incidence, predictors, and clinical significance of HBV and hepatitis C virus reactivations during chemotherapy. Materials and Methods: This prospective observational study was conducted at a tertiary care center. Hepatitis B and C virus status was identified before the initiation of cancer treatment. Liver function was monitored in all patients before each cycle of chemotherapy. Patients with deranged liver function were subjected to repeated viral antigen tests and DNA/RNA titer levels. Results: A total of 110 patients were identified as having hepatitis virus reactivation out of 1190 patients. The sites of malignancy were breast, 39.1% (43 patients); colorectal, 11.8% (13 patients); upper gastrointestinal, 10% (11 patients); ovary, 9.1% (10 patients); hematological malignancies, 8.2% (9 patients); lung, 5.6% (6 patients); genitourinary, 4.5% (5 patients); head-and-neck, 4.5% (5 patients); biliary tract, 3.6% (4 patients); brain tumor, 1.8% (2 patients); and others, 1.8% (2 patients). Most of the patients with reactivation received 5-FU/Capecitabine-based chemotherapy 37.3%, (41 patients), taxane plus platinum (10.9%, 12 patients), taxane only (10%, 11 patients), trastuzumab (8.2%, 9 patients), platinum-based (6.4%, 7 patients), tyrosine kinase inhibitors (6.4%, 7 patients), monoclonal antibodies (MABs) (3.6%, 4 patients), anthracyclines (2.7%, 3 patients), immunomodulators (2.7%, 3 patients), and other agents (11.8%, 13 patients). Conclusion: We recommend that Hepatitis B and C virus Screening must me performed before chemotherapy and that non-reactive patients should be vaccinated.

Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.

Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV). While benign in most people, EBV is responsible for infectious mononucleosis, up to 2% of human cancers, and is a trigger for the development of multiple sclerosis. Following latency establishment in B cells, EBV reactivates and is shed in saliva to enable infection of new hosts. Beyond its importance for transmission, the lytic cycle is also implicated in EBV-associated oncogenesis. Conversely, induction of lytic reactivation in latent EBV-positive tumors presents a novel therapeutic opportunity. Therefore, defining the dynamics and heterogeneity of EBV lytic reactivation is a high priority to better understand pathogenesis and therapeutic potential. In this study, we applied single-cell techniques to analyze diverse fate trajectories during lytic reactivation in three B cell models. Consistent with prior work, we find that cell cycle and MYC expression correlate with cells refractory to lytic reactivation. We further found that lytic induction yields a continuum from abortive to complete reactivation. Abortive lytic cells upregulate NFκB and IRF3 pathway target genes, while cells that proceed through the full lytic cycle exhibit unexpected expression of genes associated with cellular reprogramming. Distinct subpopulations of lytic cells further displayed variable profiles for transcripts known to escape virus-mediated host shutoff. These data reveal previously unknown and promiscuous outcomes of lytic reactivation with broad implications for viral replication and EBV-associated oncogenesis.

Reactivation of Epstein-Barr virus by n-butyric acid from Pseudoramibacter alactolyticus induces inflammatory cytokines in periapical granulomas

This study investigates whether latent Epstein-Barr virus (EBV) can be reactivated by n-butyric acid from Pseudoramibacter alactolyticus, and if such reactivation induces expression of interleukin (IL)-1β and IL-6 in periapical granulomas. We analyzed periapical granulomas and healthy gingival tissues to detect the presence of EBV and P. alactolyticus. The concentration of n-butyric acid in P. alactolyticus culture supernatants was measured. BZLF-1 luciferase assays were conducted with or without these supernatants. Immunohistochemical detection of ZEBRA-, IL-1β-, and IL-6-expressing cells was performed in the tissue samples. Additionally, mRNA expression levels of BZLF-1, IL-1β, and IL-6 were quantified and statistically analyzed for correlation. The expression of these mRNAs was also measured in Daudi cells treated with or without the culture supernatants. Both EBV and P. alactolyticus were detected in periapical granulomas, but not in healthy tissues. The concentration of n-butyric acid in the culture supernatants was ∼3.58 mmol/L. BZLF-1 luciferase activity in the presence of the culture supernatants was comparable to that of commercially available butyric acid, whereas no activity was detected without the supernatants. Cells expressing ZEBRA co-expressed IL-1β and IL-6. The mRNA levels of BZLF-1, IL-1β, and IL-6 in periapical granulomas were correlated with the number of EBV DNA copies. Daudi cells treated with the culture supernatants expressed BZLF-1, IL-1β, and IL-6 mRNA, while those without the supernatants did not. The study concludes that EBV can be reactivated by n-butyric acid produced by P. alactolyticus, leading to the induction of IL-1β and IL-6 expression in periapical granulomas.