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Virology (MD PhD) (Subject) / Metzner (Lesson)
- Common function of vmiRNAs - regulation of virus life cycle - elongation of host cell survival - evasion of the immune system - RNAi - main pathway for viral miRNAs: targeting cellular transcript with analogs
- miR-29a - cellular miRNA targeting viral transcript - detrimental for virus - modulates HIV-1 production and infectivity - targets HIV-1 mRNA for translation repression
- miR-122 - cellular miRNA targeting viral transcript - beneficial for virus - promotes Hepatitis C virus life cycle
- miR-132 - cellular miRNA targeting cellular transcript - beneficial for virus - enhances viral gene expression - Kaposi’s sarcoma- associated herpesvirus (KSHV), herpes simplex virus-1 (HSV-1) and human cytomegalovirus (HCMV)
- Maraviroc - CCR5 antagonist - (Only) antiviral drugs targeting cellular proteins Resistance pathways1. unaltered tropism (= mutations in CCR5 binding site) 2. altered tropism (= switch from CCR5 to CXCR4)
- NRTI (nucleoside reverse transcriptase inhibitor) - Antiviral drugs representing a false substrate - Herpes viruses- Hepatitis B virus Resistance:1. NRTI cannot bind anymore 2. ATP-mediated excision
- NNRTI (non nucleoside reverse transcriptase inhibitor) - Antiviral drugs targeting viral proteins - HIV: Ritonavir- Hepatitis C virus
- Zidovudine/AZT - NRTI Resistance mechanism:1. NRTI cannot bind anymore 2. ATP-mediated excision
- RNA Interference - the enzyme Dicer cleaves long double-stranded RNA (dsRNA) molecules into single-stranded RNAs (ssRNAs), the passenger strand and the guide strand. - The passenger strand is degraded and the guide strand is incorporated into the RNA-induced silencing complex (RISC). - the guide strand pairs with a complementary sequence in a messenger RNA molecule and induces cleavage by Argonaute (catalytic component of the RISC complex)
- viral miRNA targeting cell - main pathway for viral miRNAs - often 'analogs' --> mimic host effectors
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