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HSV and HCMV
| Question | Answer |
|---|---|
| Herpesvirus particle | Enveloped viral tegument strong icosahedral capsid ssDNA HSV dsDNA HCMV |
| Herpesvirus binding | gD - main receptor binding to NECTIN (conformational change) gH/gL - co-receptor gB - fusion glycoprotein |
| HSV-1 Immediate/early proteins | ICP0 ICP4 ICP22 ICP27 ICP47 |
| ICP0 IE1 | expression of all viral genes counteracts intrinsic antiviral immunity |
| ICP4 | stimulates transcription of viral genes |
| ICP22 | viral gene expression in some cell types No HCMV equivelent |
| ICP27 IE2 | nuclear export, processing of viral mRNAs |
| ICP47 | evasion of acquired immune response No HCMV equivelent |
| Early proteins required for | nuceloside metabolism DNA replication, DNA polymerase, accessory proteins viral DNA processing immune evasion |
| Late proteins required for | particle structure and assembly |
| Herpesvirus DNA replication | linear genome - circularized, dsDNA binding proteins bind at origin of replicaiton, helicase, primase and polymerase associate, replication by rolling circle amplification. |
| Capsid assembly and release | immature capsid with interior scaffold DNA enters through portal, scaffold destroyed assembles in nucleus, gains internal envelope from nuclear membrane travelling through ER, recieves final envelope with viral proteins from golgi membrane |
| Life cycle in vivo | primary infection of epithelial mucosa transport of viral capsids along axons to neural cells where they cause a latent infection establishment of latency - periodic reactivation by stress/uv. transport back down axon to primary infection site/lytic cyc |
| LATS | latent genes - only active during latency, play a modulatory role. HSV genome exists as an episome during latency. -anti-apoptotic activity -blocks expression of lytic genes -increases pool of latent cells |
| HSV diagnosis | cytopathic effect, ELISA detecting HSV antibodies, qPCR for HSV-DNA |
| Antivirals | ganciclovir, acyclovir - nucleoside analogues, incorporate into viral DNA, phosphorylated by viral thymidine kinase leading to chain termination |
| HCMV | latency in myeloid progenitor cells (Cd34+ cells) |
| HCMV symptoms | immuncompetenet - mainly asymptomatic immunocompromised - CMV disease (pneumotitis, encephalitis, hepatitis, death) Congenital HCMV - sensory defects and high mortality - 1% mother infection, 40-50% primary infection |
| HCMV and transplants | leading cause of transplant failure - 20% of haemopoetic stem cell transplants contract HCMV infection. 1. from a latent infection, 2. from transplanted organ, 3. acquired after transplant |
| HCMV diagnosis and treatments | cytopathic effect - "owls eyes" inclusion bodies, multinucleated cells ELISA for antibodies PCR for DNA Treatments - prophylactic antivirals e.g. ganciclovir but increasing resistance. use of immunoglobulin |
| Mechanisms of viral evasion | ICP47 US2 US3 US6 US10 US11 |
| ICP47 | inhibits peptide binding to TAP transporter through competitive inhibition |
| US2 and US3 | target MHC by adding ubiquitin and marking for degredation by proteosomes |
| US6 | prevents ATP binding to TAP so peptides cannot bind to MHC |
| US10 and 11 | also target MHC |
| Antibody evasion | HSV and HCMV expression glycoproteins that mimic the Fc receptors of immune cells, binding the constant end of antibodies preventing recognition by immune cells |
| Evasion of interferon response | inhibiton of IRF-3 activation (a IFN-beta promoter) shut off host protein synthesis (no ISG products) inhibits PKR activation (no phosphoylation of eif2a or apoptosis) interacts with STAT2 preventing IFN signalling cascade |
Created by:
teemo616
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