-
Viruses Jun 2024The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to a free HPV vaccine is a public health concern. HPV is one of...
The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to a free HPV vaccine is a public health concern. HPV is one of the most common sexually transmitted infections (STIs) in Nigeria, while the most known types of HPV genotypes being transmitted are the high-risk HPV-16 and 18 genotypes. In this study, we explored the predictors of self-reported HPV infections and HPV genital warts infection among a population of students, non-academic staff, and academic staff of Ibrahim Badamasi Babangida (IBB) University located in Lapai, Nigeria. We also assessed their knowledge about HPV infections and genotypes, and sexual behaviors. An online cross-sectional study was conducted by setting up a structured questionnaire on Google Forms and it was distributed to the university community via Facebook and other social media platforms of the university. The form captured questions on HPV infection, and knowledge about HPV infection and genotypes, as well as the sexual health of the participants. All variables were described using frequencies and percentage distribution; chi-squared test statistics were used to explore the association between HPV infection (medical records of HPV infection) and the participants' profile, and a logistic regression analysis was performed to examine the factors associated with HPV genital warts infection among the population. This study reveals those participants between the ages of 26-40 years (81.3%) and those currently not in a sexually active relationship-single/divorced (26.4%)-who have self-reported having the HPV-16 and -18 genotypes. Moreover, participants between 26-40 years of age (OR: 0.45, 95%CI: 0.22-0.89) reported themselves to be carriers of HPV genital warts. Therefore, this study reveals the factors associated with HPV infection and genital warts peculiar to IBB university students and staff. Hence, we suggest the need for HPV awareness programs and free HPV vaccine availability at IBB university.
Topics: Humans; Cross-Sectional Studies; Male; Female; Condylomata Acuminata; Nigeria; Students; Universities; Adult; Young Adult; Self Report; Papillomavirus Infections; Health Knowledge, Attitudes, Practice; Adolescent; Surveys and Questionnaires; Sexual Behavior; Genotype; Risk Factors; Papillomaviridae
PubMed: 38932194
DOI: 10.3390/v16060902 -
Viruses May 2024Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host...
Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and function. We previously characterized HERV-K HML-9 in the human genome. However, the biological function of this type of element in the genome of the chimpanzee, which is the closest living relative of humans, largely remains elusive. Therefore, the current study aims to characterize HML-9 in the chimpanzee genome and to compare the results with those in the human genome. Firstly, we report the distribution and genetic structural characterization of the 26 proviral elements and 38 solo LTR elements of HML-9 in the chimpanzee genome. The results showed that the distribution of these elements displayed a non-random integration pattern, and only six elements maintained a relatively complete structure. Then, we analyze their phylogeny and reveal that the identified elements all cluster together with HML-9 references and with those identified in the human genome. The HML-9 integration time was estimated based on the 2-LTR approach, and the results showed that HML-9 elements were integrated into the chimpanzee genome between 14 and 36 million years ago and into the human genome between 18 and 49 mya. In addition, conserved motifs, cis-regulatory regions, and enriched PBS sequence features in the chimpanzee genome were predicted based on bioinformatics. The results show that pathways significantly enriched for ERV LTR-regulated genes found in the chimpanzee genome are closely associated with disease development, including neurological and neurodevelopmental psychiatric disorders. In summary, the identification, characterization, and genomics of HML-9 presented here not only contribute to our understanding of the role of ERVs in primate evolution but also to our understanding of their biofunctional significance.
Topics: Animals; Pan troglodytes; Endogenous Retroviruses; Phylogeny; Humans; Terminal Repeat Sequences; Evolution, Molecular; Genome; Genome, Human; Proviruses; Virus Integration; Retroelements
PubMed: 38932184
DOI: 10.3390/v16060892 -
Viruses May 2024We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to...
We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test, and one more for p16/Ki67 dual-stain cytology. A total of 4499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% had a positive HR HPV-PCR result. Dual staining with p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Out of the PCR results that were positive for any of these HR HPV subtypes, n 68.3%, we did not find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR to avoid unnecessary colposcopies. The encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists. Therefore, we still believe that colposcopy continues to be a preferred procedure over the dual-staining protocol.
Topics: Humans; Female; Mexico; Uterine Cervical Neoplasms; Papillomavirus Infections; Molecular Diagnostic Techniques; Papanicolaou Test; Biomarkers, Tumor; Papillomaviridae; Cyclin-Dependent Kinase Inhibitor p16; Vaginal Smears; Colposcopy; Gynecology; Adult; Middle Aged; Ki-67 Antigen; Polymerase Chain Reaction; Early Detection of Cancer; Private Practice
PubMed: 38932179
DOI: 10.3390/v16060887 -
Viruses May 2024The viral interferon regulatory factors (vIRFs) of KSHV are known to dysregulate cell signaling pathways to promote viral oncogenesis and to block antiviral immune...
The viral interferon regulatory factors (vIRFs) of KSHV are known to dysregulate cell signaling pathways to promote viral oncogenesis and to block antiviral immune responses to facilitate infection. However, it remains unknown to what extent each vIRF plays a role in gene regulation. To address this, we performed a comparative analysis of the protein structures and gene regulation of the four vIRFs. Our structure prediction analysis revealed that despite their low amino acid sequence similarity, vIRFs exhibit high structural homology in both their DNA-binding domain (DBD) and IRF association domain. However, despite this shared structural homology, we demonstrate that each vIRF regulates a distinct set of KSHV gene promoters and human genes in epithelial cells. We also found that the DBD of vIRF1 is essential in regulating the expression of its target genes. We propose that the structurally similar vIRFs evolved to possess specialized transcriptional functions to regulate specific genes.
Topics: Humans; Interferon Regulatory Factors; Herpesvirus 8, Human; Epithelial Cells; Viral Proteins; Gene Expression Regulation, Viral; Promoter Regions, Genetic; Transcription, Genetic; Genome, Viral; Cell Line
PubMed: 38932139
DOI: 10.3390/v16060846 -
Viruses May 2024Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte...
Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte entry. Hepatocellular carcinoma (HCC) ranks third in global cancer deaths, yet HDV's involvement remains uncertain. Among 300 HBV-associated HCC serum samples from Taiwan's National Health Research Institutes, 2.7% (8/300) tested anti-HDV positive, with 62.7% (5/8) of these also HDV RNA positive. Genotyping revealed HDV-2 in one sample, HDV-4 in two, and two samples showed mixed HDV-2/HDV-4 infection with RNA recombination. A mixed-genotype infection revealed novel mutations at the polyadenylation signal, coinciding with the ochre termination codon for the L-HDAg. To delve deeper into the possible oncogenic properties of HDV-2, the predominant genotype in Taiwan, which was previously thought to be less associated with severe disease outcomes, an HDV-2 cDNA clone was isolated from HCC for study. It demonstrated a replication level reaching up to 74% of that observed for a widely used HDV-1 strain in transfected cultured cells. Surprisingly, both forms of HDV-2 HDAg promoted cell migration and invasion, affecting the rearrangement of actin cytoskeleton and the expression of epithelial-mesenchymal transition markers. In summary, this study underscores the prevalence of HDV-2, HDV-4, and their mixed infections in HCC, highlighting the genetic diversity in HCC as well as the potential role of both forms of the HDAg in HCC oncogenesis.
Topics: Carcinoma, Hepatocellular; Hepatitis Delta Virus; Humans; Liver Neoplasms; Genetic Variation; Genotype; Male; Middle Aged; Carcinogenesis; Female; Taiwan; Evolution, Molecular; Virus Replication; Phylogeny; RNA, Viral; Hepatitis D; Aged; Hepatitis B virus
PubMed: 38932110
DOI: 10.3390/v16060817 -
Medicina (Kaunas, Lithuania) Jun 2024: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia...
: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. : This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. : An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. : This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries.
Topics: Humans; Female; Serbia; Papillomavirus Infections; Adult; Retrospective Studies; Genotype; Prevalence; Middle Aged; Adolescent; Papillomaviridae; Uterine Cervical Neoplasms; Young Adult; Aged
PubMed: 38929539
DOI: 10.3390/medicina60060922 -
Medicina (Kaunas, Lithuania) May 2024: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoproliferative disease associated with the human T-cell lymphotropic virus type I (HTLV-1).... (Observational Study)
Observational Study
: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoproliferative disease associated with the human T-cell lymphotropic virus type I (HTLV-1). ATLL is a rare disease, found more frequently in HTLV-1-endemic areas, Romania being one of them. Despite treatment advances, the prognosis remains dismal. We aimed to describe the clinical, biological, and survival outcome features of Romanian patients with aggressive-type ATLL. We report the data of a prospective, observational, and unicentric study of all 20 patients diagnosed with lymphoma and acute types of ATLL at our center over the past 12 years. Data were collected from the patients' medical records. : Lymphoma-type ATLL (60%) was more common than acute-type ATLL (40%). Median age at diagnosis was 40.5 years, and most patients were female. Laboratory data revealed significant differences between acute and lymphoma-type ATLL, namely, higher leukocyte ( = 0.02) and lymphocyte counts ( = 0.02) and higher levels of corrected calcium ( = 0.001) in acute-type ATLL. All patients received chemotherapy, and only two underwent allogeneic stem cell transplantation. Only six patients obtained a complete or partial response to chemotherapy, mostly the lymphoma-type ones. The median survival for all patients was 6.37 months, with higher survival in the lymphoma-type ATLL (8.16 months) than in the acute-type (3.60 months). Normal calcium levels ( = 0.011), uric acid ( = 0.005), BUN score ( = 0.000), JCOG-PI moderate risk ( = 0.038), and obtaining complete or partial response ( = 0.037) were associated with higher survival. : Aggressive-type ATLL among Romanian patients presents distinct characteristics, including younger age at diagnosis, female predominance, and higher incidence of lymphoma-type ATLL compared to currently reported data. Survival remains very low, with all subtypes experiencing a median survival of less than one year.
Topics: Humans; Female; Leukemia-Lymphoma, Adult T-Cell; Male; Adult; Middle Aged; Romania; Prospective Studies; Human T-lymphotropic virus 1; HTLV-I Infections; Aged; Survival Analysis; Endemic Diseases; Prognosis
PubMed: 38929489
DOI: 10.3390/medicina60060872 -
Genes Jun 2024Human endogenous retroviruses (HERVs) are DNA transposable elements that have integrated into the human genome via an ancestral germline infection. The potential... (Review)
Review
Human endogenous retroviruses (HERVs) are DNA transposable elements that have integrated into the human genome via an ancestral germline infection. The potential importance of HERVs is underscored by the fact that they comprise approximately 8% of the human genome. HERVs have been implicated in the pathogenesis of neurodegenerative diseases, a group of CNS diseases characterized by a progressive loss of structure and function of neurons, resulting in cell death and multiple physiological dysfunctions. Much evidence indicates that HERVs are initiators or drivers of neurodegenerative processes in multiple sclerosis and amyotrophic lateral sclerosis, and clinical trials have been designed to target HERVs. In recent years, the role of HERVs has been explored in other major neurodegenerative diseases, including frontotemporal dementia, Alzheimer's disease and Parkinson's disease, with some interesting discoveries. This review summarizes and evaluates the past and current research on HERVs in neurodegenerative diseases. It discusses the potential role of HERVs in disease manifestation and neurodegeneration. It critically reviews antiretroviral strategies used in the therapeutic intervention of neurodegenerative diseases.
Topics: Humans; Endogenous Retroviruses; Neurodegenerative Diseases; Amyotrophic Lateral Sclerosis; Animals
PubMed: 38927681
DOI: 10.3390/genes15060745 -
Genes May 2024Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles...
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma. The oncogene product Tax of HTLV-I is thought to play crucial roles in leukemogenesis by promoting proliferation of the virus-infected cells through activation of growth-promoting genes. These genes code for growth factors and their receptors, cytokines, cell adhesion molecules, growth signal transducers, transcription factors and cell cycle regulators. We show here that Tax activates the gene coding for coactivator-associated arginine methyltransferase 1 (CARM1), which epigenetically enhances gene expression through methylation of histones. Tax activated the gene and increased protein expression, not only in human T-cell lines but also in normal peripheral blood lymphocytes (PHA-PBLs). Tax increased R17-methylated histone H3 on the target gene , concomitant with increased expression of CARM1. Short hairpin RNA (shRNA)-mediated knockdown of CARM1 decreased Tax-mediated induction of and gene expression, reduced E2F activation and inhibited cell cycle progression. Tax acted via response elements in intron 1 of the gene, through the NF-κB pathway. These results suggest that Tax-mediated activation of the gene contributes to leukemogenic target-gene expression and cell cycle progression, identifying the first epigenetic target gene for Tax-mediated trans-activation in cell growth promotion.
Topics: Humans; Protein-Arginine N-Methyltransferases; Gene Products, tax; Human T-lymphotropic virus 1; Cyclin D2; Transcriptional Activation; Interleukin-2 Receptor alpha Subunit; NF-kappa B; Histones; Epigenesis, Genetic; Jurkat Cells
PubMed: 38927636
DOI: 10.3390/genes15060698 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the changes of Notch signaling molecules and Th22 cells in adult patients with infectious mononucleosis (IM), and assess the regulatory function of Notch...
OBJECTIVE
To investigate the changes of Notch signaling molecules and Th22 cells in adult patients with infectious mononucleosis (IM), and assess the regulatory function of Notch signaling inhibition to Th22 cells.
METHODS
Forty-two IM patients and twenty-one healthy controls were enrolled in this study. Their peripheral blood was collected, from which plasma and peripheral blood mononuclear cells (PBMCs) were isolated. Plasma interleukin (IL)-17 and IL-22 were measured by enzyme-linked immunosorbent assay. The percentages of CD3 CD4 IL-17 Th17 cells and CD3 CD4 IL-22 Th22 cells were investigated by flow cytometry. The mRNA relative levels corresponding to Th17 transcription factor retinoic acid related orphan receptor γt (RORγt), Th22 transcription factor aryl hydrocarbon receptor (AhR), and Notch signaling pathway molecules (including Notch receptors, Notch ligands, Notch downstream molecules) were semi-quantified by real-time PCR. CD4 T cells were purified and stimulated with γ-secretase inhibitor (GSI). Cellular proliferation, Th17 and Th22 percentage, IL-17 and IL-22 secretion, transcription factor mRNA were measured in response to GSI stimulation.
RESULTS
The relative expression levels of and mRNA in PBMCs of IM group were 13.58±3.18 and 4.73±1.16, respectively, which were significantly higher than 1.09±0.12 and 1.07±0.15 in PBMCs of control group (both < 0.001). However, there were no significant differences in relative expression levels of and mRNA between IM group and control group ( >0.05). The relative expression levels of Notch ligands (including and ) mRNA and Notch downstream molecules (including and ) were increased in IM group compared with control group (all < 0.001). In IM group, the Th17 and Th22 percentage were 5.03%±1.15% and 4.48%±1.29%, respectively, which were both higher than 4.36%±0.82% and 3.83%±0.55% in control group (both < 0.05). In IM group, the IL-17 and IL-22 level were (301.1±53.82) and (101.2±16.45) pg/ml, respectively, which were both higher than (237.2±72.18) and (84.75±11.83) pg/ml in control group (both < 0.001). In IM group, the relative expression levels of and mRNA were 1.25±0.22 and 1.21±0.12, respectively, which were both higher than 0.99±0.15 and 1.04±0.11 in control group (both < 0.001). There were no remarkable differences in CD4 T cell proliferation, Th17 percentage, IL-17 secretion, and relative expression level of mRNA between cells with GSI stimulation and without GSI stimulation ( >0.05). GSI stimulation reduced Th22 percentage, IL-22 secretion, and relative expression level of mRNA compared with non-stimulation (all < 0.05).
CONCLUSION
Notch signaling pathway regulates IL-22 secretion by CD4 T cells via AhR in IM patients. Notch-AhR-Th22 pathway may take part in the pathogenesis of IM.
Topics: Humans; Signal Transduction; Adult; Th17 Cells; Receptors, Notch; Interleukin-17; Interleukin-22; Nuclear Receptor Subfamily 1, Group F, Member 3; Infectious Mononucleosis; Interleukins; Herpesvirus 4, Human; Leukocytes, Mononuclear; Receptor, Notch1; Receptors, Aryl Hydrocarbon; CD4-Positive T-Lymphocytes
PubMed: 38926989
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.041