RESUMEN
Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma-associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV-1 TAT protein can be essential in developing AIDS-associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV-specific TAT profile among PLHIV who developed KS.
Asunto(s)
Coinfección , Infecciones por VIH , Herpesvirus Humano 8 , Sarcoma de Kaposi , Productos del Gen tat del Virus de la Inmunodeficiencia Humana , Humanos , Sarcoma de Kaposi/virología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Masculino , Herpesvirus Humano 8/genética , Femenino , Adulto , Persona de Mediana Edad , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genética , Coinfección/virología , Coinfección/tratamiento farmacológico , VIH-1/genética , VIH-1/efectos de los fármacos , Variación Genética , Carga Viral , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4RESUMEN
Among several autoimmune diseases, one of the main risk factors is the female gender, and much consideration has been given to the involvement of female hormones in their etiology. B-cell activating factor (BAFF) is a key factor in survival and maturation of B cells and is overexpressed in several autoimmune patients although the mechanism behind this feature is unclear. In murine models, BAFF expression could be upregulated by exogenous estrogen treatment in splenocytes; however, no evidence of this relationship was available in humans. Here, leukocytes from healthy male and female individuals were collected and cultivated in the presence or absence of estrogen or progesterone. BAFF gene expression was accessed by quantitative PCR and compared between treated and untreated group of cells. In the presence of estrogen, BAFF expression was upregulated by more than 5 times in both genders. When exposed to progesterone, the female-originated cells showed increased expression, while the cells of male origin a significant downregulation of BAFF. Our results suggest that female hormones can modulate the expression of BAFF, a key cytokine in autoimmune pathways, in human immune cells. These data might contribute to the understanding of the etiology as well as the gender bias featured by several autoimmune disorders.