Rabbit Anti-Human SAMHD1 (a.a. 256-370) Polyclonal antibody

Introduction. Aicardi-Goutieres syndrome is a rare progressive subacute encephalopathy of early onset - generally in the first year of life - characterised by psychomotor retardation, microcephaly, alterations in the white matter of the brain, intracranial calcifications, pleocytosis and elevated levels of interferon alpha in the cerebrospinal fluid. It is associated to an increase in the expression of genes stimulated by interferon in peripheral blood, a fact known as the interferon signature. The levels of genes stimulated by interferon has been postulated as a good biomarker, as they remain high in peripheral blood over time and are more sensitive, in comparison to determinations of interferon alpha and neopterins in cerebrospinal fluid, which descend as of one year of life. To date, mutations have been reported in seven genes that overstimulate the interferon alpha pathway, and the last to be discovered is IFIH1 (interferon induced with helicase C domain 1), with a pattern of dominant autosomal inheritance. Case report. We present the first case reported in the Hispanic literature caused by a de novo mutation in the IFIH1 gene. The clinical features, studies conducted and review of the clinical, neuroradiological and genetic aspects are described. Conclusions. The inheritance of the mutations reported for Aicardi-Goutieres syndrome was classically considered as being recessive autosomal, but these findings show that dominant autosomal mutations in the IFIH1 gene can cause the disease. As a previously unreported neuroimaging finding, it presents a lesion consisting in cystic encephalomalacia in the pons.

Human SAMHD1 (hSAMHD1) restricts HIV-1 infection in non-dividing cells by depleting intracellular dNTPs to limit viral reverse transcription. Phosphorylation of hSAMHD1 at threonine (T) 592 by cyclindependent kinase (CDK) 1 and CDK2 negatively regulates HIV-1 restriction. Mouse SAMHD1 (mSAMHD1) restricts HIV-1 infection in non-dividing cells, but whether its phosphorylation regulates retroviral restriction is unknown. Here we identified six phospho-sites of mSAMHD1, including T634 that is homologous to T592 of hSAMHD1 and phosphorylated by CDK1 and CDK2. We found that wild-type (WT) mSAMHD1 and a phospho-ablative mutant, but not a phospho-mimetic mutant, restricted HIV-1 infection in differentiated U937 cells. Murine leukemia virus (MLV) infection of dividing NIH3T3 cells was modestly restricted by mSAMHD1 WT and phospho-mutants, but not by a. dNTPase-defective mutant. Our results suggest that phosphorylation of mSAMHD1 at T634 by CDK1/2 negatively regulates its HIV-1 restriction in differentiated cells, but does not affect its MLV restriction in dividing cells. (C) 2015 Elsevier Inc. All rights reserved.