Cytokeratin-17 expression is commonly observed in keratinocytic skin tumours and controls tissue homeostasis impacting HPV protein expression.

BACKGROUND: The structured expression of several keratins in the skin is associated with differentiation status of the epidermal layers, whereas others are upregulated only during wound healing, in skin disorders and in cancers. One of these stress keratins, K17, is correlated with poor prognosis in various cancer types and its loss has been shown to decelerate tumour growth. K17 expression can also be detected in cutaneous squamous cell carcinomas (SCCs), where UV-irradiation and infection with cutaneous human papillomaviruses (HPVs) are important co-factors. It was previously reported that K17 is upregulated in papillomavirus (PV)-induced benign skin lesions in mice and induces an immunological status that is beneficial for tumour growth. OBJECTIVES: In order to investigate whether K17 upregulation is induced by PVs, we analysed K17 levels in skin tumour specimens of different animal models and humans. METHODS: Various immunofluorescence stainings were performed to identify K17 expression as well as levels of E-Cadherin, vimentin and CD271. Tissues were further analysed by PCRs, qPCRs and ELISA to control for PV activity. K17knockdown cells were generated and effects on viral life cycle were investigated by infection assays, qPCR and Western blotting. RESULTS: We could show that K17 is commonly expressed in skin tumours and that its presence is not directly linked to viral oncoprotein expression. Rather, K17 expression seems to be a marker of epithelial differentiation and its absence in tumour tissue is associated with an epithelial-to-mesenchymal transition. We further showed that the absence of K17 in skin tumours increases markers of cancer stem-like cells and negatively affects viral protein synthesis. CONCLUSIONS: Collectively, our data indicate that K17 expression is a common feature in skin tumourigenesis. While it is not primarily targeted by PV oncoproteins, our in vivo and in vitro data suggest that it is an important regulator of epithelial differentiation and thus may play a role in controlling viral protein synthesis.

HPV8-induced STAT3 activation led keratinocyte stem cell expansion in human actinic keratoses.

Despite epidermal turnover, the skin is host to a complex array of microbes, including viruses, such as HPV, which must infect and manipulate skin keratinocyte stem cells (KSCs) to survive. This crosstalk between the virome and KSC populations remains largely unknown. Here, we investigated the effect of HPV8 on KSCs using various mouse models. We observed that the HPV8 early region gene E6 specifically caused Lrig1+ hair follicle junctional zone KSC proliferation and expansion, which would facilitate viral transmission. Within Lrig1+ KSCs specifically, HPV8 E6 bound intracellular p300 to phosphorylate the STAT3 transcriptional regulatory node. This induced ΔNp63 expression, resulting in KSC expansion into the overlying epidermis. HPV8 was associated with 70% of human actinic keratoses. Together, these results define the "hit-and-run" mechanism for HPV8 in human actinic keratosis as an expansion of KSCs, which lack melanosome protection and are thus susceptible to sun light-induced malignant transformation.

Interplay between HIV and Human Pegivirus (HPgV) Load in Co-Infected Patients: Insights from Prevalence and Genotype Analysis.

Human pegivirus (HPgV) is transmitted through sexual or parenteral exposure and is common among patients receiving blood products. HPgV is associated with lower levels of human immunodeficiency virus (HIV) RNA and better survival among HIV-infected patients. This study aimed to investigate the prevalence of HPgV and determine its subtypes in HIV-infected individuals living in Istanbul, which has the highest rate of HIV infection in Türkiye. Total RNA extraction from plasma, cDNA synthesis, and nested PCR were performed for HPgV on plasma samples taken from 351 HIV-1-infected patients. The HPgV viral load was quantified on HPgV-positive samples. HPgV genotyping was performed by sequencing the corresponding amplicons. In the present study, the overall prevalence of HPgV RNA in HIV-infected patients was 27.3%. HPgV subtypes 1, 2a, and 2b were found, with subtype 2a being the most frequent (91.6%). Statistical analysis of HIV-1 viral load on HPgV viral load showed an opposing correlation between HIV-1 and HPgV loads. In conclusion, these data show that HPgV infection is common among HIV-positive individuals in Istanbul, Türkiye. Further comprehensive studies are needed to clarify both the cellular and molecular pathways of these two infections and to provide more information on the effect of HPgV on the course of the disease in HIV-infected individuals.

Syphilis seroprevalence among HlV-infected males in Istanbul, Turkey / Seroprevalencia de la sífilis entre hombres infectados con el HIV en Estambul, Turquía

Abstract Syphilis has become a serious issue for human immunodeficiency virus (HIV)-infected patients worldwide in recent years; however, the studies related to HIV coinfection and syphilis reinfections in Istanbul, Turkey, are limited. Ourobjective was to determine the seroprevalence of syphilis among HIV-infected men in the city which has one of the highest HIV prevalence rates in Turkey. Two hundred and forty four (244) HIV-positive men were evaluated at Istanbul Medical Faculty, Department of Medical Microbiology from March to June 2018. Serum samples were screened for the presence of antibodies against Treponema pallidum using the chemilumines-cent microparticle immunoassay (CMIA). Samples found to be positive were investigated with the rapid plasma reagin (RPR) test and the T. pallidum hemagglutination assay (TPHA). The patients completed a questionnaire for sociodemographic data. The mean age was found to be 41.8 years; 35.6% were men who havesexwith men (MSM). The overall seroprevalence of syphilis among the patients was 19.3%. MSM had a significantly higher seroprevalence than heterosexual patients (28.7%). In Turkey, there is a high seroprevalence of syphilis in HIV-infected patients, MSM being the most affected group. Therefore, HIV-infected patients should be screened for syphilis at least annually and should be informed about sexually transmitted diseases (STDs).

Resumen En los últimos años, la sífilis se ha convertido en un problema grave para los pacientes infectados por el virus de la inmunodeficiencia humana (HIV) en todo el mundo; sin embargo, los estudios relacionados con la coinfección por HIV y las reinfecciones por sífilis en Estambul, Turquía, son limitados. Nuestro objetivo fue determinar la seroprevalencia de la sífilis entre los hombres infectados por el HIV en Estambul, ciudad con las tasas de prevalencia del HIV más altas de Turquía. Se evaluaron 244 hombres con HIV entre marzo y junio de 2018 en la Facultad de Medicina de Estambul, Departamento de Microbiología Médica. Las muestras de suero se analizaron para detectar la presencia de anticuerpos contra Treponema pallidum con un inmunoensayo de micropartículas quimioluminiscentes (CMIA). Las muestras que resultaron positivas en dicha prueba se investigaron con la prueba de reagina plasmática rápida (RPR) y el ensayo de hemoaglutinación T. pallidum (TPHA). Los pacientes completaron un cuestionario de datos sociodemográficos. La media de la edad fue de 41,8 anos; 35,6% eran hombres que tienen sexo con hombres (HSH). La seroprevalencia global de sífilis entre los pacientes fue del 19,3%. Los HSH tuvieron una seroprevalencia significativamente mayor que los pacientes heterosexuales (28,7%). En Turquía, existe una alta seroprevalencia de la sífilis en pacientes infectados por el HIV y los HSH son el grupo más afectado. Por lo tanto, los pacientes infectados por el HIV deben someterse a la detección de sífilis al menos una vez al año y deben ser informados sobre las enfermedades de transmisión sexual (ETS).