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Virology (MD PhD) (Fach) / Hale (Lektion)
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- Amantadine blocks M2 - viruses still bind to cells and are internalised. - viruses undergo membrane fusion with host endosomes. - NO viral RNA segments are released – infection does not proceed.
- Oseltamivir = Tamiflu blocks NA - Inhibits neuraminidase by mimicking sialic acid. - virus particles do not egress from the cell.
- Zanamivir = Relenza blocks NA - Inhibits neuraminidase by mimicking sialic acid. - virus particles do not egress from the cell.
- Influenza A virus genome replication - in the nucleus! 1. Virus needs cellular mRNAs for transcription (cap-snatching mechanism) 2. Virus needs cellular splicing machinery to expand mRNA repertoire
- Intrinsic Immunity - Requires no previous contact with a pathogen.- Requires no virus-triggered signaling (can be upregulated though). - Cell-autonomous and ‘ready-to-go’ systems that:• Directly create an antiviral state in the infected cell.• Lead to death of the infected cell.• Recognise infection and signal to neighbouring cells (IFNs).
- Autophagy = mechanism for sequestration and subsequent lysosomal degradation. - Facilitates the removal of intracellular materials not degraded through the ubiquitin-proteasome pathway. - Triggered usually by metabolic or translational stresses. - Does not result in cell death – allows the cell to ‘weather the storm’ of infection.
- Viral Inhibition of Autophagy Viruses inhibit macroautophagy at two checkpoints: 1. Herpes viruses interfere with autophagosome formation. 2. Influenza A virus and HIV block autophagosome fusion with endosomes and/or lysosomes.
- IFN-induced antiviral effectors APOBEC3G - inhibits reverse transcriptase and integration Viruses:- HIV- Hepatitis B virus
- IFN-induced antiviral effectors TRIM5a - blocks uncoating of incoming virion- promotes innate immune signalling by sensing retroviral capsid Viruses:- HIV
- IFN-induced antiviral effectors Tetherin - blocks release of enveloped viruses Viruses:- HIV- Filovirus (Ebola)- Arenavirus - Herpesvirus - basal expression level, upregulated by IFN
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- IFN-induced antiviral effectors SAMDH1 - inhibits HIV replication in myeloid cells by decreasing dNTP supply - basal expression level, upregulated or activated by IFN
- IFN-induced antiviral effectors TREX1 - removes cytosolic nonproductive reverse-transcribed DNA- inhibits innate immune responses to HIV
- IFN-induced antiviral effectors IFITM family - blocks cytosolic entry Viruses:- Influenza virus- Dengue virus- West Nile virus --> genetic determinant for outcome of a influenza virus infections in humans - basal expression level, upregulated or activated by IFN
- IFN-induced antiviral effectors Mx - blocks transcription - The expression of MxA strictly depends on IFN.- Human MxB is expressed at basal levels in some cell types and is upregulated by IFN. - Influenza virus NP is the target of MxA (resistance can be transferred with NP protein --> pandemic potential) - MxA against Influenza- MxB against HIV
- IFN-induced antiviral effectors PKR - inhibits virus translation by protein phosphorylation - apoptotic - many RNA viruses