RESUMEN
HIV replication is limited by cellular restriction factors, such as APOBEC and tetherin, which themselves are counteracted by viral proteins. SAMHD1 was recently identified as a novel HIV restriction factor in myeloid cells, and was shown to be blocked by the lentiviral protein Vpx. SAMHD1 limits viral replication through an original mechanism: it hydrolyses intracellular dNTPs in non-cycling cells, thus decreasing the amount of these key substrates, which are required for viral DNA synthesis. In this Progress article, we describe how SAMHD1 regulates the pool of intracellular nucleotides to control HIV replication and the innate immune response.
Asunto(s)
Infecciones por VIH/inmunología , VIH-1/fisiología , Proteínas de Unión al GTP Monoméricas/inmunología , Animales , Enfermedades Autoinmunes del Sistema Nervioso/genética , Desoxirribonucleótidos/inmunología , Desoxirribonucleótidos/metabolismo , Silenciador del Gen , VIH-1/inmunología , VIH-1/metabolismo , VIH-1/patogenicidad , Interacciones Huésped-Patógeno , Humanos , Inmunidad Innata/inmunología , Ratones , Proteínas de Unión al GTP Monoméricas/química , Proteínas de Unión al GTP Monoméricas/genética , Proteínas de Unión al GTP Monoméricas/metabolismo , Malformaciones del Sistema Nervioso/genética , Proteína 1 que Contiene Dominios SAM y HD , Proteínas Reguladoras y Accesorias Virales , Replicación Viral/inmunologíaRESUMEN
The dinucleotide dpTpA held electrostatically on DEAE cellulose was used as an affinity column for the purification of dpTpA specific antibodies. Chromatography of the gamma-globulin fraction from dpTpA specific antisera on this column resulted in the retention of dpTpA specific antibodies which were later eluted along with the bound dpTpA using 1M NaCl. Dextran coated charcoal was the method of choice for the dissociation and removal of dpTpA bound to the antibodies. This method may extend itself to the purification of antibodies specific for other oligonucleotides.