👤 C S Tailor

We investigated mRNA expression of 49 nuclear hormone receptors (NRs) and 35 transcriptional coregulators in mouse bone marrow-derived dendritic cells (DCs) upon infection with Newcastle Disease virus (NDV) or murine cytomegalovirus (MCMV). These viruses regulated mRNA expression of some NRs among which NOR1 and LXRα were highly induced at mRNA and protein levels. Exogenous expression of the latter NRs repressed IRF3- or IRF7-induced transactivation of the interferon β promoter and NDV infection further potentiated their repressive effect. The viral infection also significantly regulated mRNA expression of some coregulators, including HDAC1. Toll-like receptor ligands regulated NR and coregulator mRNA expression similar to the viruses. Thus, NRs and coregulators are integral components of DC-organizing anti-viral response wherein NOR1 and LXRα participate in regulating interferon production. Show less

Xenotropic and polytropic murine leukemia viruses (X-MLVs and P-MLVs) cross-interfere to various extents in non-mouse species and in wild Asian mice, suggesting that they might use a common receptor for infection. Consistent with this hypothesis, the susceptibility of some wild mice to X-MLVs has been mapped to the P-MLV receptor locus at the distal end of mouse chromosome 1. In this study, we report the isolation and characterization of a cDNA for the human X-MLV cell surface receptor (X-receptor) by using a human T lymphocyte cDNA library in a retroviral vector. The predicted X-receptor contains 696 amino acids with multiple hydrophobic potential membrane-spanning sequences and with weak homologies to the yeast proteins SYG1, of unknown function, and PHO81, which has been implicated in a system that regulates transport of inorganic phosphate. Expression of the X-receptor in Chinese hamster ovary cells, which are substantially resistant to P-MLVs and to X-MLVs, made them susceptible to both of these virus groups. The mouse homologue of the X-receptor was mapped by hybridization to the distal end of chromosome 1 at the same position as the P-MLV receptor gene Rmc1. These results strongly support the hypothesis that a common gene encodes the receptors for X-MLVs and P-MLVs, with the human X-receptor preferentially mediating X-MLV infections and the homologous protein of inbred mice mediating only P-MLV infections. We propose that X-MLVs and P-MLVs comprise a single family of retroviruses that have coevolved in response to diversification in X-receptor genes of the host. Show less