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PLoS Pathogens Jun 2024Reactivation from latency plays a significant role in maintaining persistent lifelong Epstein-Barr virus (EBV) infection. Mechanisms governing successful activation and...
Reactivation from latency plays a significant role in maintaining persistent lifelong Epstein-Barr virus (EBV) infection. Mechanisms governing successful activation and progression of the EBV lytic phase are not fully understood. EBV expresses multiple viral microRNAs (miRNAs) and manipulates several cellular miRNAs to support viral infection. To gain insight into the host miRNAs regulating transitions from EBV latency into the lytic stage, we conducted a CRISPR/Cas9-based screen in EBV+ Burkitt lymphoma (BL) cells using anti-Ig antibodies to crosslink the B cell receptor (BCR) and induce reactivation. Using a gRNA library against >1500 annotated human miRNAs, we identified miR-142 as a key regulator of EBV reactivation. Genetic ablation of miR-142 enhanced levels of immediate early and early lytic gene products in infected BL cells. Ago2-PAR-CLIP experiments with reactivated cells revealed miR-142 targets related to Erk/MAPK signaling, including components directly downstream of the B cell receptor (BCR). Consistent with these findings, disruption of miR-142 enhanced SOS1 levels and Mek phosphorylation in response to surface Ig cross-linking. Effects could be rescued by inhibitors of Mek (cobimetinib) or Raf (dabrafenib). Taken together, these results show that miR-142 functionally regulates SOS1/Ras/Raf/Mek/Erk signaling initiated through the BCR and consequently, restricts EBV entry into the lytic cycle.
Topics: Humans; Herpesvirus 4, Human; MicroRNAs; Virus Activation; Epstein-Barr Virus Infections; CRISPR-Cas Systems; Virus Latency; Burkitt Lymphoma; Cell Line, Tumor
PubMed: 38885264
DOI: 10.1371/journal.ppat.1011970 -
Immune escape of avian oncogenic Marek's disease herpesvirus and antagonistic host immune responses.NPJ Vaccines Jun 2024Marek's disease virus (MDV) is a highly pathogenic and oncogenic alpha herpesvirus that causes Marek's disease (MD), which is one of the most important immunosuppressive... (Review)
Review
Marek's disease virus (MDV) is a highly pathogenic and oncogenic alpha herpesvirus that causes Marek's disease (MD), which is one of the most important immunosuppressive and rapid-onset neoplastic diseases in poultry. The onset of MD lymphomas and other clinical diseases can be efficiently prevented by vaccination; these vaccines are heralded as the first demonstration of a successful vaccination strategy against a cancer. However, the persistent evolution of epidemic MDV strains towards greater virulence has recently resulted in frequent outbreaks of MD in vaccinated chicken flocks worldwide. Herein, we provide an overall review focusing on the discovery and identification of the strategies by which MDV evades host immunity and attacks the immune system. We have also highlighted the decrease in the immune efficacy of current MD vaccines. The prospects, strategies and new techniques for the development of efficient MD vaccines, together with the possibilities of antiviral therapy in MD, are also discussed.
PubMed: 38879650
DOI: 10.1038/s41541-024-00905-0 -
Virology Journal Jun 2024Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the...
BACKGROUND
Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the cellular immune response of patients with different EBV-associated diseases or different courses of the same disorder requires interrogation of a maximum number of EBV antigens. Here, we tested three novel EBV-derived antigen formulations for their ability to reactivate virus-specific T cells ex vivo in patients with EBV-associated infectious mononucleosis (IM).
METHODS
We comparatively analyzed EBV-specific CD4+ and CD8+ T-cell responses to three EBV-derived antigen formulations in 20 pediatric patients during the early phase of IM: T-activated EBV proteins (BZLF1, EBNA3A) and EBV-like particles (EB-VLP), both able to induce CD4+ and CD8+ T-cell responses ex vivo, as well as an EBV-derived peptide pool (PP) covering 94 well-characterized CD8+ T-cell epitopes. We assessed the specificity, magnitude, kinetics, and functional characteristics of EBV-specific immune responses at two sequential time points (v1 and v2) within the first six weeks after IM symptom onset (T).
RESULTS
All three tested EBV-derived antigen formulations enabled the detection of EBV-reactive T cells during the early phase of IM without prior T-cell expansion in vitro. EBV-reactive CD4+ and CD8+ T cells were mainly mono-functional (CD4+: mean 64.92%, range 56.15-71.71%; CD8+: mean 58.55%, range 11.79-85.22%) within the first two weeks after symptom onset (v1) with IFN-γ and TNF-secreting cells representing the majority of mono-functional EBV-reactive T cells. By contrast, PP-reactive CD8+ T cells were primarily bi-functional (>60% at v1 and v2), produced IFN-γ and TNF and had more tri-functional than mono-functional components. We observed a moderate correlation between viral load and EBNA3A, EB-VLP, and PP-reactive CD8+ T cells (r = 0.345, 0.418, and 0.356, respectively) within the first two weeks after T, but no correlation with the number of detectable EBV-reactive CD4+ T cells.
CONCLUSIONS
All three EBV-derived antigen formulations represent innovative and generic recall antigens suitable for monitoring EBV-specific T-cell responses ex vivo. Their combined use facilitates a thorough analysis of EBV-specific T-cell immunity and allows the identification of functional T-cell signatures linked to disease development and severity.
Topics: Humans; Infectious Mononucleosis; Antigens, Viral; Herpesvirus 4, Human; Child; CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Female; Male; Adolescent; Child, Preschool; Epitopes, T-Lymphocyte
PubMed: 38877590
DOI: 10.1186/s12985-024-02411-0 -
BMC Women's Health Jun 2024The primary screening technique for precancerous lesions and cervical cancer is human papillomavirus (HPV) testing, and HPV self-sampling has been shown to be consistent...
The levels of women's awareness, experience, acceptability and preference for Vaginal Human Papillomavirus (HPV) self-sampling in three provinces of China: a cross-sectional study.
BACKGROUND
The primary screening technique for precancerous lesions and cervical cancer is human papillomavirus (HPV) testing, and HPV self-sampling has been shown to be consistent with clinician sampling in terms of the accuracy of the results and may improve cervical cancer screening rates. The aim of this study was to understand the level of awareness, experience, acceptability, and preference for vaginal HPV self-sampling among women in Jiangsu, Zhejiang, and Shanghai, China, and to analyze the possible influencing factors to determine the feasibility of implementing self-sampling.
METHODS
Overall, 1793 women were included in the data analysis. A self-administered questionnaire was utilized. In addition to descriptive analysis, univariate and multivariate analyses were used to explore the associations between sociodemographic features, history of cervical cancer screening, and the level of awareness, experience, acceptability, and preference for HPV self-samples.
RESULTS
The participants' level of awareness of and experience with HPV self-sampling were moderate. A total of 88.8% of participants rated the acceptability as "high", and self-sampling was preferred by 64.2% of them for cervical cancer screening. People aged 45 to 54 years showed a preference for both clinician sampling(OR = 1.762 (1.116-2.163)) and self-sampling (OR = 1.823 (1.233-2.697)). Those who had graduated from high school or above (OR = 2.305 (1.517-3.503), OR = 2.432 (1.570-3.768), OR = 3.258 (2.024-5.244)) preferred clinician-sampling, and those with a bachelor's degree or above (OR = 1.664 (1.042-2.657)) preferred self-sampling. Middle- and high-income individuals showed no preference for either sampling method (OR < 1).
CONCLUSIONS
HPV self-sampling is widely accepted, but awareness, experience and preferences need to be improved. These results may help to adjust public health strategies for the early inclusion of HPV self-sampling as a screening method in national initiatives to prevent cervical cancer.
Topics: Humans; Female; China; Middle Aged; Adult; Cross-Sectional Studies; Papillomavirus Infections; Uterine Cervical Neoplasms; Health Knowledge, Attitudes, Practice; Early Detection of Cancer; Patient Acceptance of Health Care; Surveys and Questionnaires; Patient Preference; Specimen Handling; Vaginal Smears; Self Care; Young Adult; Aged; Papillomaviridae; Human Papillomavirus Viruses
PubMed: 38877469
DOI: 10.1186/s12905-024-03186-w -
Scientific Reports Jun 2024Kaposi's sarcoma (KS) is a cancer affecting skin and internal organs for which the Kaposi's sarcoma associated herpesvirus (KSHV) is a necessary cause. Previous work has...
Kaposi's sarcoma (KS) is a cancer affecting skin and internal organs for which the Kaposi's sarcoma associated herpesvirus (KSHV) is a necessary cause. Previous work has pursued KS diagnosis by quantifying KSHV DNA in skin biopsies using a point-of-care (POC) device which performs quantitative loop-mediated isothermal amplification (LAMP). These previous studies revealed that extracting DNA from patient biopsies was the rate limiting step in an otherwise rapid process. In this study, a simplified, POC-compatible alkaline DNA extraction, ColdSHOT, was optimized for 0.75 mm human skin punch biopsies. The optimized ColdSHOT extraction consistently produced 40,000+ copies of DNA per 5 µl reaction from 3 mg samples-a yield comparable to standard spin column extractions-within 1 h without significant equipment. The DNA yield was estimated sufficient for KSHV detection from KS-positive patient biopsies, and the LAMP assay was not affected by non-target tissue in the unpurified samples. Furthermore, the yields achieved via ColdSHOT were robust to sample storage in phosphate-buffered saline (PBS) or Tris-EDTA (TE) buffer prior to DNA extraction, and the DNA sample was stable after extraction. The results presented in this study indicate that the ColdSHOT DNA extraction could be implemented to simplify and accelerate the LAMP-based diagnosis of Kaposi's sarcoma using submillimeter biopsy samples.
Topics: Humans; DNA, Viral; Herpesvirus 8, Human; Biopsy; Skin; Sarcoma, Kaposi; Nucleic Acid Amplification Techniques; Point-of-Care Systems; Molecular Diagnostic Techniques
PubMed: 38877073
DOI: 10.1038/s41598-024-64533-3 -
Frontiers in Public Health 2024Limited data exist on HPV prevalence and genotyping during the COVID-19 pandemic. A total of 130,243 samples from 129, 652 women and 591 men who visited the First...
Limited data exist on HPV prevalence and genotyping during the COVID-19 pandemic. A total of 130,243 samples from 129, 652 women and 591 men who visited the First People's Hospital of Linping District between 2016 and 2022 were recruited. HPV genotypes were detected by polymerase chain reaction (PCR) amplification and nucleic acid molecular hybridization. Then the prevalence characteristics of HPV genotypes and trends in HPV infection rates from 2016 to 2022 were analyzed. Results showed that among the study population, the overall prevalence of HPV infection was 15.29%, with 11.25% having single HPV infections and 4.04% having multiple HPV infections, consistent with previous findings. HPV genotypes exhibited similar distribution patterns in both male and female groups, with HPV16, HPV52, HPV58, HPV18, and HPV39 being the most prevalent. Age-related analysis unveiled a bimodal pattern in HPV prevalence, with peaks in infection rates observed in individuals below 20 and those aged 61-65 years. Comparing the pre- and during COVID-19 periods revealed significant disparities in HPV infections, with variations in specific HPV genotypes, including 16, 18, 35, 45, 52, 58, 59, and 68. This study provides valuable insights into the prevalence, distribution, and epidemiological characteristics of HPV infections in a large population. It also highlights the potential impact of the COVID-19 pandemic on HPV trends.
Topics: Humans; COVID-19; Papillomavirus Infections; Female; China; Male; Prevalence; Middle Aged; Adult; Genotype; Aged; Papillomaviridae; Young Adult; SARS-CoV-2; Adolescent; Pandemics
PubMed: 38873306
DOI: 10.3389/fpubh.2024.1357311 -
PloS One 2024The genotype distribution of human papillomavirus (HPV) infection varies greatly in different regions. This study aims to determine the prevalence and type-specific...
PURPOSE
The genotype distribution of human papillomavirus (HPV) infection varies greatly in different regions. This study aims to determine the prevalence and type-specific distribution of HPV among females from Chengdu and Aba in Sichuan Province, which differ in geographical location, economic status, and living habits. These can serve as evidence of epidemic patterns for future design and implementation of vaccination and screening programs.
METHODS
A retrospective cross-sectional study was conducted on 144 113 women who underwent cervical screening at Chengdu Women's and Children's Central Hospital from January 2015 to September 2020. Meanwhile, 1799 samples from February 2018 to December 2021 were collected from Aba Maternal and Child Health Hospital. HPV DNA genotype testing was performed using real-time PCR. The overall prevalence, annual trend, age-specific prevalence, and type distribution were analyzed.
RESULTS
The overall HPV prevalence was 22.51% in Chengdu. During 2015-2020, the highest prevalence rate was observed in 2018. Age-specific HPV distribution displayed a bimodal distribution among women aged ≤25 or ≥46 years old. The top three prevalent genotypes were HPV52, -16, and -58. Although the total prevalence of HPV in Aba was 14.23%, there was an upward trend from 2018 to 2021. However, no significant differences were identified in HPV infection rate across all age groups. HPV52, -53, and -16 were the major genotypes. Furthermore, single-type HPV infections and high-risk HPV infections were identified as the most common infection types in both regions.
CONCLUSION
Our findings demonstrate the overall prevalence of HPV was still high in Chengdu and Aba. The age-specific prevalence distribution demonstrated different patterns. Non-vaccine-covered HR-HPV53, -51and LR-HPV81, -CP8304 were frequently detected, which was worth significant clinical attention. In summary, regional HPV screening provides valuable clinical guidance for cervical cancer prevention and vaccine selection in Western China.
Topics: Humans; Female; China; Papillomavirus Infections; Adult; Prevalence; Middle Aged; Cross-Sectional Studies; Retrospective Studies; Papillomaviridae; Young Adult; Genotype; Uterine Cervical Neoplasms; DNA, Viral; Cervix Uteri
PubMed: 38870122
DOI: 10.1371/journal.pone.0304760 -
Current Opinion in Virology Jun 2024Oncogenic viruses contribute to 15% of global human cancers. To achieve that, virus-encoded oncoproteins deregulate cellular transcription, antagonize common cellular... (Review)
Review
Oncogenic viruses contribute to 15% of global human cancers. To achieve that, virus-encoded oncoproteins deregulate cellular transcription, antagonize common cellular pathways, and thus drive cell transformation. Notably, adenoviruses were the first human viruses proven to induce cancers in diverse animal models. Over the past decades, human adenovirus (HAdV)-mediated oncogenic transformation has been pivotal in deciphering underlying molecular mechanisms. Key adenovirus oncoproteins, encoded in early regions 1 (E1) and 4 (E4), co-ordinate these processes. Among the different adenovirus species, the most extensively studied HAdV-C5 displays lower oncogenicity than HAdV-A12. A complete understanding of the different HAdV-A12 and HAdV-C5 oncoproteins in virus-mediated cell transformation, as summarized here, is relevant for adenovirus research and offers broader insights into viral transformation and oncogenesis.
PubMed: 38865835
DOI: 10.1016/j.coviro.2024.101413 -
Revista Do Instituto de Medicina... 2024Women living with human immunodeficiency virus are at an increased risk of developing cancers related to human papillomavirus (HPV). Thus, it is important to combine...
Women living with human immunodeficiency virus are at an increased risk of developing cancers related to human papillomavirus (HPV). Thus, it is important to combine clinical assessments, serological screening, and HPV data for planning prevention policies. This study aimed to identify HPV and its specific types in the cervical, anal, and oral mucosa of HIV-seropositive women, associating it with viral load and lymphocyte count. Sociodemographic characteristics, health data (CD4+ and CD8+ T cell counts and viral load), and biological samples (cervical, anal, and oral) were collected from 86 HIV-positive women undergoing antiretroviral therapy. Data were classified according to the presence or absence of HPV-DNA, HPV-DNA presence at one or more anatomic sites, and level of oncogenic risk, considering low- and high-risk oncogenic HPV-DNA groups. The presence of HPV in the cervicovaginal site was 65.9%, 63.8% in anal canal, and 4.2% in oral mucosa. A viral load ≥75 HIV copies/mL was associated with the presence of HPV-DNA. There was an association between viral load and the low-risk HPV or high-risk HPV groups. We found a high prevalence of HPV infection in HIV-seropositive women, particularly in the cervical and anal mucosa, with viral load ≥75 HIV copies/mL being associated with HPV-DNA presence.
Topics: Humans; Female; Viral Load; Papillomavirus Infections; Adult; HIV Infections; DNA, Viral; Cervix Uteri; Papillomaviridae; Middle Aged; Lymphocyte Count; Mouth Mucosa; Anal Canal; Prevalence; Cross-Sectional Studies; Socioeconomic Factors; CD4 Lymphocyte Count; Risk Factors; Human Papillomavirus Viruses
PubMed: 38865574
DOI: 10.1590/S1678-9946202466036 -
Frontiers in Immunology 2024Across the wide range of clinical conditions, there exists a sex imbalance where biological females are more prone to autoimmune diseases and males to some cancers.... (Review)
Review
Across the wide range of clinical conditions, there exists a sex imbalance where biological females are more prone to autoimmune diseases and males to some cancers. These discrepancies are the combinatory consequence of lifestyle and environmental factors such as smoking, alcohol consumption, obesity, and oncogenic viruses, as well as other intrinsic biological traits including sex chromosomes and sex hormones. While the emergence of immuno-oncology (I/O) has revolutionised cancer care, the efficacy across multiple cancers may be limited because of a complex, dynamic interplay between the tumour and its microenvironment (TME). Indeed, sex and gender can also influence the varying effectiveness of I/O. Androgen receptor (AR) plays an important role in tumorigenesis and in shaping the TME. Here, we lay out the epidemiological context of sex disparity in cancer and then review the current literature on how AR signalling contributes to such observation via altered tumour development and immunology. We offer insights into AR-mediated immunosuppressive mechanisms, with the hope of translating preclinical and clinical evidence in gender oncology into improved outcomes in personalised, I/O-based cancer care.
Topics: Animals; Female; Humans; Male; Immunotherapy; Neoplasms; Receptors, Androgen; Sex Factors; Signal Transduction; Treatment Outcome; Tumor Microenvironment
PubMed: 38863718
DOI: 10.3389/fimmu.2024.1416941