RESUMO
Viroporins constitute a class of viral membrane proteins with diverse roles in the viral life cycle. They can self-assemble and form pores within the bilayer that transport substrates, such as ions and genetic material, that are critical to the viral infection cycle. However, there is little known about the oligomeric state of most viroporins. Here, we use native mass spectrometry in detergent micelles to uncover the patterns of oligomerization of the full-length SARS-CoV-2 envelope (E) protein, poliovirus VP4, and HIV Vpu. Our data suggest that the E protein is a specific dimer, VP4 is exclusively monomeric, and Vpu assembles into a polydisperse mixture of oligomers under these conditions. Overall, these results revealed the diversity in the oligomerization of viroporins, which has implications for the mechanisms of their biological functions as well as their potential as therapeutic targets.
Assuntos
COVID-19 , Infecções por HIV , Poliovirus , Humanos , SARS-CoV-2/metabolismo , Proteínas Viroporinas , Proteínas Virais Reguladoras e Acessórias , Proteínas do Vírus da Imunodeficiência Humana/química , Proteínas do Vírus da Imunodeficiência Humana/metabolismoRESUMO
Natural Killer (NK) cells have the potential to eliminate HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC). NK cell activation is tightly regulated by the engagement of its inhibitory and activating receptors. The activating receptor CD16 drives ADCC upon binding to the Fc portion of antibodies; NK cell activation is further sustained by the co-engagement of activating receptors NTB-A and 2B4. During HIV-1 infection, Nef and Vpu accessory proteins contribute to ADCC escape by downregulating the ligands of NTB-A and 2B4. HIV-1 also evades ADCC by keeping its envelope glycoproteins (Env) in a "closed" conformation which effectively masks epitopes recognized by non-neutralizing antibodies (nnAbs) which are abundant in the plasma of people living with HIV. To achieve this, the virus uses its accessory proteins Nef and Vpu to downregulate the CD4 receptor, which otherwise interacts with Env and exposes the epitopes recognized by nnAbs. Small CD4-mimetic compounds (CD4mc) have the capacity to expose these epitopes, thus sensitizing infected cells to ADCC. Given the central role of NK cell co-activating receptors NTB-A and 2B4 in Fc-effector functions, we studied their contribution to CD4mc-mediated ADCC. Despite the fact that their ligands are partially downregulated by HIV-1, we found that both co-activating receptors significantly contribute to CD4mc sensitization of HIV-1-infected cells to ADCC.
Assuntos
Citotoxicidade Celular Dependente de Anticorpos , Anticorpos Anti-HIV , Infecções por HIV , HIV-1 , Células Matadoras Naturais , Família de Moléculas de Sinalização da Ativação Linfocitária , Humanos , Citotoxicidade Celular Dependente de Anticorpos/imunologia , HIV-1/imunologia , Células Matadoras Naturais/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Família de Moléculas de Sinalização da Ativação Linfocitária/imunologia , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Antígenos CD4/imunologia , Antígenos CD4/metabolismo , Proteínas do Vírus da Imunodeficiência Humana/imunologia , Proteínas do Vírus da Imunodeficiência Humana/metabolismo , Produtos do Gene nef do Vírus da Imunodeficiência Humana/imunologia , Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo , Proteínas Virais Reguladoras e Acessórias/metabolismo , Proteínas Virais Reguladoras e Acessórias/imunologia , Proteínas Virais Reguladoras e Acessórias/genética , Anticorpos Neutralizantes/imunologia , Proteínas ViroporinasRESUMO
Existen evidencias que apuntan a la existencia de una asociación inversa entre la ingesta de proteínas vegetales y la presión arterial. En este estudio, los datos de adolescentes VIH +, que acuden a la consulta del Centro de Atención a Pacientes con Enfermedades Infectocontagiosas "Dra. Elsa La Corte" (CAPEI) de la Universidad Central de Venezuela (UCV), fueron analizados para estudiar la relación entre el consumo de proteínas vegetales y la presión arterial tanto sistólica como diastólica, ajustando por índice de masa corporal (IMC) y consumo de energía. Estudio transversal en 43 adolescentes VIH+ con edades entre 15 y 18 años en ambos sexos, que acudieron al CAPEI en el año 2009. Se analizó la media de dos lecturas obtenidas con 5 minutos de intervalo en una visita. Se determinaron peso y altura y se calculó el IMC. Para la determinación de la ingesta de proteínas vegetales se aplicó la técnica de recordatorio de 24 horas. El análisis estadístico se basó en el modelo de regresión lineal. Los resultados muestran una asociación negativa y significativa entre el consumo de proteínas vegetales y la presión arterial sistólica y diastólica, después de ajustar por consumo de energía e IMC, las diferencias de presión arterial sistólica y diastólica asociada con una ingesta de proteínas vegetales de 57,6 kilocalorías por ciento (variación intercuartil) fue de -2,8 mm Hg y -2,4 mm Hg, respectivamente (p <0,05 para ambos). La promoción y planificación de dietas con altos contenidos de proteínas vegetales puede ser de utilidad para prevenir y controlar valores elevados de la presión arterial
Data are available that indicate an independent inverse relationship of dietary vegetable protein to blood pressure (BP). In this investigation data from HIV adolescents attending CAPEI/UCV, were analyzed to study the relationship between dietary vegetable protein and systolic/diastolic pressures, with control for body mass index (BMI) and calorie intake. This was a cross-sectional study with 43 HIV adolescents 15 to 18 years of age. BP was measured 2 times at 1 visit; height and weight were measured, and BMI was calculated; dietary data were obtained from 24-hour dietary recalls. Multivariate regression was applied.The results showed that with control for BMI and calorie intake, estimated average BP differences associated with a vegetable protein intake that was higher by 57,6 %kcal (interquartile range) were -2,8 mm Hg systolic and -2,4 mm Hg diastolic (p <0,05 both). Broad improvement in diets high in vegetable protein can be important in preventing and controlling high blood pressure