Heterogeneous nuclear ribonucleoprotein K promotes cap-independent translation initiation of retroviral mRNAs.

Translation initiation of the human immunodeficiency virus-type 1 (HIV-1) genomic mRNA (vRNA) is cap-dependent or mediated by an internal ribosome entry site (IRES). The HIV-1 IRES requires IRES-transacting factors (ITAFs) for function. In this study, we evaluated the role of the heterogeneous nuclear ribonucleoprotein K (hnRNPK) as a potential ITAF for the HIV-1 IRES. In HIV-1-expressing cells, the depletion of hnRNPK reduced HIV-1 vRNA translation. Furthermore, both the depletion and overexpression of hnRNPK modulated HIV-1 IRES activity. Phosphorylations and protein arginine methyltransferase 1 (PRMT1)-induced asymmetrical dimethylation (aDMA) of hnRNPK strongly impacted the protein's ability to promote the activity of the HIV-1 IRES. We also show that hnRNPK acts as an ITAF for the human T cell lymphotropic virus-type 1 (HTLV-1) IRES, present in the 5'UTR of the viral sense mRNA, but not for the IRES present in the antisense spliced transcript encoding the HTLV-1 basic leucine zipper protein (sHBZ). This study provides evidence for a novel role of the host hnRNPK as an ITAF that stimulates IRES-mediated translation initiation for the retroviruses HIV-1 and HTLV-1.

RNA-Binding Proteins as Regulators of Internal Initiation of Viral mRNA Translation.

Viruses are obligate intracellular parasites that depend on the host's protein synthesis machinery for translating their mRNAs. The viral mRNA (vRNA) competes with the host mRNA to recruit the translational machinery, including ribosomes, tRNAs, and the limited eukaryotic translation initiation factor (eIFs) pool. Many viruses utilize non-canonical strategies such as targeting host eIFs and RNA elements known as internal ribosome entry sites (IRESs) to reprogram cellular gene expression, ensuring preferential translation of vRNAs. In this review, we discuss vRNA IRES-mediated translation initiation, highlighting the role of RNA-binding proteins (RBPs), other than the canonical translation initiation factors, in regulating their activity.

The double-stranded RNA-binding protein, Staufen1, is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation.

Translation initiation of the viral genomic mRNA (vRNA) of human immunodeficiency virus-type 1 (HIV-1) can be mediated by a cap- or an internal ribosome entry site (IRES)-dependent mechanism. A previous report shows that Staufen1, a cellular double-stranded (ds) RNA-binding protein (RBP), binds to the 5'untranslated region (5'UTR) of the HIV-1 vRNA and promotes its cap-dependent translation. In this study, we now evaluate the role of Staufen1 as an HIV-1 IRES-transacting factor (ITAF). We first confirm that Staufen1 associates with both the HIV-1 vRNA and the Gag protein during HIV-1 replication. We found that in HIV-1-expressing cells, siRNA-mediated depletion of Staufen1 reduces HIV-1 vRNA translation. Using dual-luciferase bicistronic mRNAs, we show that the siRNA-mediated depletion and cDNA-mediated overexpression of Staufen1 acutely regulates HIV-1 IRES activity. Furthermore, we show that Staufen1-vRNA interaction is required for the enhancement of HIV-1 IRES activity. Interestingly, we find that only Staufen1 harboring an intact dsRNA-binding domain 3 (dsRBD3) rescues HIV-1 IRES activity in Staufen1 CRISPR-Cas9 gene edited cells. Finally, we show that the expression of Staufen1-dsRBD3 alone enhances HIV-1 IRES activity. This study provides evidence of a novel role for Staufen1 as an ITAF promoting HIV-1 vRNA IRES activity.

Estomatitis nicotínica asociada al hábito de fumar cigarro invertido en paciente ecuatoriana / Nicotine stomatitis associated with reverse smoking habit in Ecuadorian patient

Introducción: la estomatitis nicotínica es un trastorno benigno de la mucosa oral del paladar duro, que puede extenderse al paladar blando y que comúnmente está presente en individuos fumadores de tabaco y cigarrillo. Esta lesión se manifiesta por la presencia de pápulas blanquecinas, aplanadas y generalmente asintomáticas. Objetivo: evaluar las lesiones en paladar causadas por el hábito de fumar cigarrillo de manera invertida y los beneficios de la supresión de esta práctica. Caso: paciente de 69 años, de sexo femenino, habituada a fumar cigarro de manera invertida desde la adolescencia. Examen clínico extraoral normal. En la exploración intraoral se observó edentulismo parcial y placas blanquecinas en paladar, con un tiempo de evolución desconocido. Se realizó diagnóstico clínico e histológico de estomatitis nicotínica. Conclusiones: la paciente fue diagnosticada con estomatitis nicotínica causada por la costumbre de fumar de manera invertida, lo que convierte a este en el primer caso reportado en Ecuador. La supresión de la práctica de tabaquismo invertido permitió una recuperación de lamucosa sin secuelas.

Background: Nicotinic stomatitis is a benign disorder of the oral mucosa affecting hard palate, which may extend to the soft palate. This lesion is commonly present in tobacco and cigarette smokers. It is manifested by the presence of whitish and flattened papules, generally asymptomatic. Objetive: To evaluate palate injuries caused by the habit of inverted cigarette smoking and the benefits of suppressing this practice. Case: A 69-year-old female patient, who habitually smoked cigarettes invertedly since adolescence. Clinal examination normal. During the oral clinical examination were observed partial edentulism, whitish plates on the palate, with an unknown period of time. Clinical diagnosis and histology of nicotinic stomatitis was made. Conclusions: The patient was diagnosed with nicotine stomatitis caused by reverse smoking habit; the suppression of the reverse smoking practice allowed recovery of the mucosa without sequelae. This is the first case reported in Ecuador.

Especies del género Malassezia en piel sana de niños y adolecentes con VIH-SIDA / Malassezia species on healthy skin of children and teens with HIV / AIDS

Antecedentes: Las especies del género Malassezia forman parte de la biota cutánea normal humana y pueden ser aisladas en áreas ricas en glándulas sebáceas. Su colonización es alta durante edad prepuberal y puberal debido al aumento de actividad de dichas glándulas. Objetivo: Determinar la colonización por especies del género Malassezia en piel sana de niños y adolescentes con VIH/SIDA. Metodología: Las muestras fueron tomadas mediante el método de la impronta con cinta adhesiva transparente, en cuero cabelludo, pabellón auricular, pecho, espalda, muslo, antebrazo, palma de la mano e inoculadas en el medio con base de goma Spondia dulcis. La identificación de las especies se realizó siguiendo las claves descritas por Guého et al. Se realizó el test de difusión en tween propuesto por Guillot et al, la prueba de la catalasa, y la utilización de triptófano como fuente única de nitrógeno. Resultados: De un total de 80 niños y adolescentes, solo 23(28.75 por ciento) de ellos se les aisló Malassezia. 10 (43.48 por ciento) de sexo masculino y 13 (56.52 por ciento) de sexo femenino. Solo se encontró, Malassezia sympodialis con un predominio del 100 por ciento. Correspondiendo al mayor porcentaje de positividad al grupo etario de 4-7 años (56.52 por ciento). Las localizaciones anatómicas predominantes fueron: pabellón auricular (25.5 por ciento) seguida de pecho (21.3 por ciento) y espalda (19.1 por ciento). Conclusiones: En niños con HIV/SIDA se observa un patrón de colonización por M. sympodialis.

Background: Malassezia species are part of the normal human skin biota and can be isolated from different body areas, mainly those rich in sebaceous glands. Colonization is high during prepuberal and puberal for the increased activity of the sebaceous glands. Aims: Determine the colonization by Malassezia species in healthy skin of children and teenagers with HIV/AIDS. Methods: Samples were taken using imprint method with transparent adhesive tape, were taken from scalp, ear, chest, back, thigh, forearm and palm; were inoculated in Spondias dulcis medium. The species identification was performed according the instructions described by Guého et al, Tween diffusion test proposed by Guillot et al, catalase test, and the use of tryptophan as only source of nitrogen. Results: From a total of 80 children and teenagers, only 23 (28.75 percent) of them were isolated Malassezia. 10 (43.48 percent) were from males and 13 (56.52 percent) from females. Found only Malassezia sympodialis with a prevalence of 100 percent. Corresponding to the higher percentage of positivity the age group 4-7 years (56.52 percent). The predominant anatomical locations were: ear (25.5 percent) followed by chest (21.3 percent) and back (19.1 percent) respectively. Conclusions: In children with HIV / AIDS colonization pattern observed is the present of M. sympodialis.