inteferons and how viruses evade them Flashcards
CpG and ZAP
viruses that have a high level of CPG are detected in the body by a ZAP protein in our body, which cuts the CPG- CPG needed for replication, so they can’t replicate
type 1 interferons- what they are and functions
polypeptides released from infected cells- cause an antiviral state in infected and neighbouring cells (ie they produce interferon stimulated genes), and enhanced innate and adaptive response
types of type 1 interferons- cells that produces them, what triggers them, and how many types
IFN beta produced by all cells, triggered by IRF-3, IFN alpha produced by dendritic cells, triggered by IR-F7: only 1 type of IFN beta, 13 types of IFNalpha
type 2 interferons
INF gamma- produced by T cells and NK cells, which affect adaptive immune response
type 3 interferons
interferon lamda (upside down Y)- important at epithelial cells
how innate immune system senses pathogens and types of PRR’S
PAMPS (pathogen associated molecular patterns), detected PRR’S (pattern recognition receptors), such as RLRS (RIG like receptors), TLRS (toll like receptors), which sense foreign RNA in cytoplasm, as well as cGAS (senses foreign DNA)
how RLRS work
sense foreign RNA, and activates MAVS, which phosphorylates IRF3, which goes from cytoplasm into nucleus to switch on INF beta gene ie IRF3 acts as a T.F
how TLRS work
they work in ENDOSOMES (viruses can enter via endosomes)- when they sense viral RNA, TLR3 activates IRF3, TLR7 activates IRF7, which produces both INF beta and alpha gene
DNA sensor- CGAS
senses foreign DNA, which activates IRF3 via STING pathway= switches on INFalpha/beta
effect of type 1 IFN
bind to IFNAR (IFN alpha) receptors on both its OWN cell (autocrine signalling) and neighbouring cells (paracrine), switching on MANY IFN stimulated genes
what occurs in herpes simplex encephalitis
lack of INF alpha/beta within CNS in response to HSV
inteferon stimulated genes-
protein kinase R- inhibits translation (thus virus can’t replicate), serpine (activates proteases), IFITM3 (inhibits viruses entering via ENDOSOMES)
issue with IFN stimulated genes and solution
these genes are toxic to the cell, but MORE toxic to virus- SOCS gene turns off these genes
how viruses evade IFN response with examples of INF induction blockage
hide their PAMP, activate SOCS, affect protein synthesis (ie can’t produce INF stimulated gene proteins), stop INF production eg Hep C cleaves MAVS using NS3 protease, influenza binds to RLR using NS1 protease
POX viruses
large DNA viruses which have accessory genes that modify immune response- they do this by producing cytokine receptors, which bind to cytokines like IFN, preventing them from working