Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The type I interferon response protects cells against invading viral pathogens. The cellular factors that mediate this defence are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified since their discovery more than 25 years ago, only a few have been characterized with respect to antiviral activity. For most ISG products, little is known about their antiviral potential, their target specificity and their mechanisms of action. Using an overexpression screening approach, here we show that different viruses are targeted by unique sets of ISGs. We find that each viral species is susceptible to multiple antiviral genes, which together encompass a range of inhibitory activities. To conduct the screen, more than 380 human ISGs were tested for their ability to inhibit the replication of several important human and animal viruses, including hepatitis C virus, yellow fever virus, West Nile virus, chikungunya virus, Venezuelan equine encephalitis virus and human immunodeficiency virus type-1. Broadly acting effectors included IRF1, C6orf150 (also known as MB21D1), HPSE, RIG-I (also known as DDX58), MDA5 (also known as IFIH1) and IFITM3, whereas more targeted antiviral specificity was observed with DDX60, IFI44L, IFI6, IFITM2, MAP3K14, MOV10, NAMPT (also known as PBEF1), OASL, RTP4, TREX1 and UNC84B (also known as SUN2). Combined expression of pairs of ISGs showed additive antiviral effects similar to those of moderate type I interferon doses. Mechanistic studies uncovered a common theme of translational inhibition for numerous effectors. Several ISGs, including ADAR, FAM46C, LY6E and MCOLN2, enhanced the replication of certain viruses, highlighting another layer of complexity in the highly pleiotropic type I interferon system.
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PMID:A diverse range of gene products are effectors of the type I interferon antiviral response. 2615 58

Macrophages act as reservoirs of human immunodeficiency virus type 1 (HIV-1) and play an important role in its transmission to other cells. HIV-1 Vpr is a multi-functional protein involved in HIV-1 replication and pathogenesis; however, its exact role in HIV-1-infected human macrophages remains poorly understood. In this study, we used a microarray approach to explore the effects of HIV-1 Vpr on the transcriptional profile of human monocyte-derived macrophages (MDMs). More than 500 genes, mainly those involved in the innate immune response, the type I interferon pathway, cytokine production, and signal transduction, were differentially regulated (fold change >2.0) after infection with a recombinant adenovirus expressing HIV-1 Vpr protein. The differential expression profiles of select interferon-stimulated genes (ISGs) and genes involved in the innate immune response, including STAT1, IRF7, MX1, MX2, ISG15, ISG20, IFIT1, IFIT2, IFIT3, IFI27, IFI44L, APOBEC3A, DDX58 (RIG-I), TNFSF10 (TRAIL), and RSAD2 (viperin) were confirmed by real-time quantitative PCR and were consistent with the microarray data. In addition, at the post-translational level, HIV-1 Vpr induced the phosphorylation of STAT1 at tyrosine 701 in human MDMs. These results demonstrate that HIV-1 Vpr leads to the induction of ISGs and expand the current understanding of the function of Vpr and its role in HIV-1 immune pathogenesis.
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PMID:HIV-1 Vpr induces interferon-stimulated genes in human monocyte-derived macrophages. 2517 Aug 34

As cancer mortality is high in most regions of the world, early screening of cancer has become increasingly important. Minimally invasive screening programs that use peripheral blood mononuclear cells (PBMCs) are a new and reliable strategy that can achieve early detection of tumors by identifying marker genes. From 797 datasets, four (GSE12771, GSE24536, GSE27562, and GSE42834) including 428 samples, 236 solid tumor cases, and 192 healthy controls were chosen according to the inclusion criteria. A total of 285 genes from among 440 reported genes were selected by meta-analysis. Among them, 4 of the top significantly differentially expressed genes (ANXA1, IFI44, IFI44L, and OAS1) were identified as marker genes of PBMCs. Pathway enrichment analysis identified, two significant pathways, the 'primary immunodeficiency' pathway and the 'cytokine-cytokine receptor interaction' pathway. Protein- protein interaction (PPI) network analysis revealed the top 27 hubs with a degree centrality greater than 23 to be hub genes. We also identified 3 modules in Molecular Complex Detection (MCODE) analysis: Cluster 1 (related to ANXA1), Cluster 2 (related to IFI44 and IFI44L) and Cluster 3 (related to OAS1). Among the 4 marker genes, IFI44, IFI44L, and OAS1 are potential diagnostic biomarkers, even though their results were not as remarkable as those for ANXA1 in our study. ANXA1 is involved in the immunosuppressive mechanism in tumor-bearing hosts and may be used in a new strategy involving the use of the host's own immunity to achieve tumor suppression.
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PMID:Identification of human peripheral blood monocyte gene markers for early screening of solid tumors. 3222 26