RESUMO
Soluble factors from CD8(+) T cells and cervicovaginal mucosa of women are recognized as important in controlling human immunodeficiency virus type 1 (HIV-1) infection and transmission. Previously, we have shown the strong anti-HIV-1 activity of prothymosin α (ProTα) derived from CD8(+) T cells. ProTα is a small acidic protein with wide cell distribution, to which several functions have been ascribed, depending on its intracellular or extracellular localization. To date, activities of ProTα have been attributed to a single protein known as isoform 2. Here we report the isolation and identification of 2 new ProTα variants from CD8(+) T cells and cervicovaginal lavage with potent anti-HIV-1 activity. The first is a splice variant of the ProTα gene, known as isoform CRA_b, and the second is the product of a ProTα gene, thus far classified as a pseudogene 7. Native or recombinant ProTα variants potently restrict HIV-1 replication in macrophages through the induction of type I interferon. The baseline expression of interferon-responsive genes in primary human cervical tissues positively correlate with high levels of intracellular ProTα, and the knockdown of ProTα variants by small interfering RNA leads to downregulation of interferon target genes. Overall, these findings suggest that ProTα variants are innate immune mediators involved in immune surveillance.
Assuntos
Líquidos Corporais/química , Linfócitos T CD8-Positivos/metabolismo , HIV-1/efeitos dos fármacos , Interferon Tipo I/metabolismo , Precursores de Proteínas/metabolismo , Timosina/análogos & derivados , Replicação Viral/efeitos dos fármacos , Sequência de Aminoácidos , Fármacos Anti-HIV/farmacologia , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Interferon beta/genética , Interferon beta/metabolismo , Interferons , Interleucinas/genética , Interleucinas/metabolismo , Macrófagos , Dados de Sequência Molecular , Precursores de Proteínas/genética , Timosina/genética , Timosina/metabolismo , Replicação Viral/fisiologiaRESUMO
A prospective, single-blinded, randomized trial was initiated to determine whether injection site pain differed in adolescents receiving two concentrations of 150 mg of depot medroxyprogesterone acetate (DMPA). Ninety-five adolescents seeking injectable contraception were randomized to receive 150 mg of DMPA as follows: a deltoid injection of 1.0 mL from a single-unit-dose vial containing 150 mg/mL or 0.38 mL from a multidose vial containing 400 mg/mL of DMPA. A visual analogue scale was measured at each visit and cumulatively compared between the groups. Continuation rates were tabulated. The report of pain for the multidose vial group was significantly higher than for the unit-dose vial group (p<.003). The dropout rates for both groups were high at 1 year and were not statistically different (multidose group=64% and unit-dose group=77%). Twenty percent of the subjects in the multidose group vs. 22% in the unit-dose group discontinued due to bleeding irregularities. The concentrated form of DMPA led to greater pain at the injection site than did the less concentrated form, but this did not lead to higher discontinuation rates among adolescents.
