Studies on the interaction of HSV-1 multifunctional protein ICP27 with the nuclear pore complex proteins

Herpes simplex virus (HSV-1) ICP27 is a multifunctional immediate early (IE) protein, required for expression of several early and late genes and acts at transcriptional and posttranscriptional levels. ICP27 contains both a nuclear localization signal and a nuclear export signal and shuttles between the nucleus and the cytoplasm. It interacts directly with various cellular proteins including REF and cellular mRNA export receptor TAP to export viral mRNAs. However other transport mechanisms may also be employed. All transport across the nuclear envelope must occur via the nuclear pore complex, which consists of proteins called nucleoporins (NUPs). NUPs act to regulate the transport cargos by interaction with mRNA bound proteins and transport receptors, karyopherins. To further explore the transport requirements for ICP27 and viral mRNA export, we investigated its direct interaction with nucleoporins and show that ICP27 interacts directly with nucleoporins tested, in vitro and in wild type and mutant virus infected cells and from RNase I treated and untreated cell extracts indicating that this interaction is not mediated via RNA. Implications of this interaction is discussed in this thesis

Increasing Awareness of Papillomaviruses and Their Association with Human Diseases

The papillomavirus family is known to be responsible for a quarter of virus-related cancers worldwide. High-risk types are the causative agents of anogenital, cervical and various cancers of the mouth, throat, intestines, vagina, penis and anus. Cervical cancer and various other malignancies induced by papillomaviruses are a global health problem, and the growing prevalence of these diseases indicates the need to increase awareness of this viral family. In this review, published articles during 2001-2020 were searched using keywords such as Papillomavirus, Cervical Cancer and Papilloma Vaccine. Our review represents the results of the association of high-risk HPV serotypes with many malignancies in human. Furthermore, issues such as HPV vaccination, cervical cancer screening, and other preventive programs worldwide are discussed

A review on human reproductive systems encountering with the severe acute respiratory syndrome coronavirus 2 infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the leading cause of the new deadly pneumonia named coronavirus disease 2019 (COVID-19) pandemic. This pathogen has different co-receptors on various tissues, resulting in vast pathophysiological circumstances. Here, we present a comprehensive narrative review focusing on the impact of SARS-CoV2 on human reproduction. Evidence-based literature revealed inconsistent results for this virus in the reproductive organs of patients with COVID-19, even in the critical phase. Conversely, numerous satisfactory data represented those different reproductive activities, from gametogenesis to pregnancy, can be targeted by SARS-CoV2. The severity of COVID-19 depends on the differential expression of the host cellular components required to enter SARS-CoV2. The cytokine storm and oxidative stress coming out during COVID-19 are associated with complications in reproductive endocrinopathies. Men are naturally more susceptible to COVID-19, especially accompanied by orchitis and varicocele. Synergistically the interaction of SARS-CoV2 and female reproductive failures (polycystic ovary syndrome and endometriosis) increases the susceptibility to COVID-19. Thus, pharmaceutical interventions that ameliorate the complications in individuals with reproductive disorders can be helpful to achieve good outcomes in assisted reproductive techniques. Soon, an increase in the infertility rate will likely be an overall impact of SARS-CoV2 in patients who recovered from COVID-19. Key words: SARS-CoV-2, Human, Reproductive system

Clinical and Laboratory Findings of Hospitalized Patients with Influenza in Hospitals of Golestan Province

Influenza is an acute viral respiratory disease with diverse clinical manifestations. Despite extensive research, ambiguities remain regarding its prognostic factors. In this cross-sectional retrospective study, conducted during 2021 on 993 samples (546 males 447 females) from patients with suspected acute viral respiratory infections who were hospitalized in hospitals of Golestan Province, we evaluated the clinical and laboratory findings of patients with influenza. The samples were sent to the provincial molecular diagnostics laboratory for real-time polymerase chain reaction (PCR) molecular testing. All samples were also tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Test results, along with demographic, clinical, and laboratory data, were collected using a standardized questionnaire. Of the 993 samples tested for influenza, 174 were reported as positive. All, but one, of these positive cases were influenza A. From 993 tests for SARS-CoV-2, 271 cases were also reported as positive. Additionally, 11 patients had influenza and SARS-CoV-2 co-infection. The mean age of influenza patients hospitalized in the intensive care unit (ICU) was determined to be 55.60±15.11 years, while in other wards, it was 37.51±12.1 years (P<0.05). Regarding gender, the ICU-hospitalized male-to-female ratio was 3 times and 1.35 times in other wards (P<0.05). In ICU-hospitalized patients, the highest percentage of clinical symptoms belonged to fever, cough, chills, and anorexia, and in patients hospitalized in other wards, the highest percentage belonged to fever, followed by cough, chest pain, and chills. There was a statistically significant difference between ICU-hospitalized patients and those hospitalized in other wards for symptoms, such as anorexia, arthralgia, myalgia, sore throat, cough, nausea, headache, and chills (P<0.05). Blood factors, such as white blood cell (WBC) count, neutrophil and lymphocyte percentages, hemoglobin, erythrocyte sedimentation rate (ESR), and platelets, were evaluated, and no statistically significant difference was observed between the two patient groups. Biochemical factors, including blood urea nitrogen (BUN), creatinine, sodium, potassium, liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), and direct and indirect bilirubin, were also examined, and no significant difference was found between the two patient groups. Additionally, other factors, such as oxygen and carbon dioxide saturation percentages, bicarbonate, and blood pH were assessed, and a statistically significant difference was found between the two groups for oxygen and carbon dioxide saturation percentages (P<0.05). Based on the findings of this study, age and gender are effective factors in the severity of influenza. Men and older adults are at particular risk for ICU hospitalization. The high prevalence of influenza A and cases of SARS-CoV-2 co-infection also highlight the importance of accurate diagnosis and appropriate treatment. Given the increased risk of infection and disease severity among the elderly, implementing preventive programs, such as annual influenza and coronavirus disease 2019 (COVID-19) vaccinations, is essential for this group. Additionally, attention to laboratory findings like blood oxygen levels can be effective in the early identification of high-risk patients

Efficient Bayesian estimation and combination of GARCH-type models

This chapter proposes an up-to-date review of estimation strategies available for the Bayesian inference of GARCH-type models. The emphasis is put on a novel efficient procedure named AdMitIS. The methodology automatically constructs a mixture of Student-t distributions as an approximation to the posterior density of the model parameters. This density is then used in importance sampling for model estimation, model selection and model combination. The procedure is fully automatic which avoids difficult and time consuming tuning of MCMC strategies. The AdMitIS methodology is illustrated with an empirical application to S&P index log-returns where non-nested GARCH-type models are estimated and combined to predict the distribution of next-day ahead log-returns

Optimized isolation and purification of native glycoprotein B from herpes simplex virus 1: a streamlined approach

Background and Objectives: Viral membrane glycoproteins are essential for host cell recognition, membrane fusion and immune evasion, making them critical targets for antiviral therapies and vaccine development. However, their isolation in native conformation is challenging due to structural complexity and limitations of conventional purification methods. The aim of current study was to develop a cost-effective, reproducible method for the isolation and purification of glycoprotein B (gB) from Herpes Simplex Virus type 1 (HSV-1) while maintaining its native conformation for functional and interaction studies. Materials and Methods: HSV-1 particles were concentrated via ultracentrifugation and membrane proteins were extracted using a modified protocol of the Mem-PER™ Plus Membrane Protein Extraction Kit. Native PAGE with a 4-8% gradient gel was employed to isolate multimeric gB (~300 kDa), followed by electroelution to extract the protein from the gel. The purity and integrity of gB were validated using SDS-PAGE and Western blot analysis. Results: The method successfully isolated glycoprotein B in its native multimeric form with high purity and adequate concentration (0.157 mg/mL). The pH of the native gel (8.3) and the high molecular weight of gB facilitated separation from other viral surface proteins. SDS-PAGE and Western blot confirmed the specificity and structural integrity of the purified protein. Conclusion: This study introduces a cost-effective and reliable method for isolating viral glycoproteins in their native conformation. The approach offers significant advantages over traditional chromatography-based techniques, making it ideal for research-scale applications, including functional and interaction studies

An Overview of Hepatitis B Virus Surface Antigen Secretion Inhibitors

Current anti-hepatitis B virus (HBV) regimen do not meet ideal result due to emerging resistance strains, cytotoxicity, and unfavorable adverse effects. In chronic HBV infection, high rates of sub-viral particles (SVPs) bearing HBV surface antigen (HBsAg) is a major obstacle regarding to raise effective immune responses and subsequently virus clearance. Development of potent HBsAg secretion inhibitors would provide a better insight into HBV immunopathogenesis and therapy. Investigating new non-toxic HBsAg secretion inhibitors targeting either viral or cellular factors could restore the immune response to remove virally infected hepatocytes after inhibiting SVPs. In this study, we overview several classes of HBV inhibitors with focus on their limitations and advantages over anti-HBsAg secretion potential