title: [Mechanisms of retroviral immunosuppressive domain-induced immune modulation].
abstract: Immunosuppressive domains (ISD) of viral envelope glycoproteins provide highly pathogenic phenotypes of various retroviruses. ISD interaction with immune cells leads to an inhibition of a response. In the 1980s it was shown that the fragment of ISD comprising of 17 amino acids (named CKS-17) is carrying out such immune modulation. However the underlying mechanisms were not known. The years of thorough research allowed to identify the regulation of Ras-Raf-MEK-MAPK and PI3K-AKT-mTOR cellular pathways as a result of ISD interaction with immune cells. By the way, this leads to decrease of secretion of stimulatory cytokines (e.g., IL-12) and increase of inhibitory, anti-inflammatory ones (e.g., IL-10). One of the receptor tyrosine kinases inducing signal in these pathways acts as the primary target of ISD while other key regulators--cAMP and diacylglycerol (DAG), act as secondary messengers of signal transduction. Immunosuppressive-like domains can be found not only in retroviruses; the presence of ISD within Ebola viral envelope glycoproteins caused extremely hard clinical course of virus-induced hemorrhagic fever. A number of retroviral-origin fragments encoding ISD can be found in the human genome. These regions are expressed in the placenta within genes of syncytins providing a tolerance of mother's immune system to an embryo. The present review is devoted to molecular aspects of retroviral ISD-induced modulation of host immune system.
authors.forename: V M
authors.initials: VM
authors.lastname: Blinov
authors.forename: G S
authors.initials: GS
authors.lastname: Krasnov
authors.forename: A V
authors.initials: AV
authors.lastname: Shargunov
authors.forename: M A
authors.initials: MA
authors.lastname: Shurdov
authors.forename: V V
authors.initials: VV
authors.lastname: Zverev
mesh_terms: D015894:Genome, Human; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016753:Interleukin-10 / Q000235:genetics; D010455:Peptides / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D015398:Signal Transduction; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014759:Viral Envelope Proteins; D016753:Interleukin-10; C053692:CKS 17