ViralZone - Molecular biology Flashcards
Bacteriophages infect prokaryotes
How do they differ in structure to other virsues?
Typically tailed viruses
Have icosahedral head, which contains viral genome
Has tail - which includes tail tube, tail fiber, and baseplate. This allows binding to bacteria
Bacteriophage
What is role of each of these parts?
tail fiber
baseplate
tail fiber - responsible for specific attachment to host. Due to high selective pressure, tail fiber genes evolve more rapidly than other phage genes., and exchanges of genes occur via horizontal transfer
baseplate - bind to host cell receptor causing baseplate confirmational change. This initiates genome ejection, which can be due to tail sheath contraction
What theory underpins icosahedral capsid symmetry classification?
Caspar-Klug theory (CK)
What is the basis of the Caspar-Klug theory, of icoasahedral capsid symmentry?
Each icosahedron is built upon 60 identical subunits, organised in different way
T number indicates how many different proteins make up the capsid
e.g T=1 means that 1 protein makes up the entire capsid. This is the simpelst capsid
T=2 means that 2 proteins make up entire capsid. For total of 120 capsid proteins
T=3 means that 3 proteins make up entire capsid. For a total of 180 capsid proteins
How do enveloped viruses enter a cell?
Fusion at plasma membrane
Endocytosis
How do non-enveloped viruses enter a cell?
Endocytosis
Pore-mediated penetration
Cell-cell transport - syncytium/ nanotubules
Host-virus interactions
What are examples of cellular Pattern Recognition Receptors (PRR)
RIG-like Receptors (RLR) - viral RNA sensors
Toll-like Receptors (TLR) - extracellular sensors
PKR - dsRNA and stress sensor
Viral DNA sensor
RIG-like Receptors (RLR) - are viral RNA sensors
How do they work?
RLR belong to an innate sensor pathway that recognize RNA virus products and activates cellular antiviral state.
Upon viral infection, RIG-I and related RNA helicases, MDA5 and LGP2 recognize viral “foreign” RNA and trigger intracellular signaling events that induce innate immunity, the first line of defense against microbial infection.
These sentry proteins initiate a signaling cascade by interacting with the downstream partner Mitochondrial antiviral-signaling protein (MAVS), located to the mitochondria.
MAV activation results in downstream signaling, resulting in the production of cytokines and interferons, has been linked to a number of pathways that ultimately activate transcription factors IRF3, IRF7 and NF-kappa-B.
Many viral antagonists of the signaling cascade leading to interferon production have been identified. The influenza A virus NS1 protein has been shown to inhibit RIG-I through direct interaction, while paramyxovirus V protein binds and inhibits MDA5 to abrogate its signaling actions. Hepatitis viruses A, B and C affect the cascade by impairing MAVS protein. Downstream, cellular IRF3 and IRF7 can be activated by both RLR and TLR pathway, and are targeted by many viruses including Epstein-Barr virus, Ebolaviruses, Rotaviruses or Papillomaviruses.
Toll-like Receptors (TLR) are extracellular sensors of viruses
How do they work?
TLR are transmembrane glycoproteins
Activated by viral products and by endogenous cellular products released during inflammation of nearby cells
Results in production of cytokines, IFN
Protein Kinase R (PKR) - dsRNA and stress sensor
How does it work?
PKR is activated by viral dsRNA, dimerizes, autophosphorylates and then phosphorylates the eIF2-alpha translation initiation factor
eIF2 alpha phosphorylation results in arrest of translation of both cellular and viral mRNAs.
Many viruses inhibit PKR activity
Infected cells have dsDNA sensors, apart from PKR
What is an example of this?
STING pathway - located on endoplasmic reticulum.
Responds to dsDNA present in viruses/ bacteria
Activated STING protects infected cells by mediating the phosphorylation of the transcription factor interferon regulatory factor 3 (IRF3), which in turn induces the synthesis of type I interferon, leading to reduction of viral titers.
IFN produced by virally infected cell
What pathway does this activate?
JAK-STAT signalling cascade
Results in expression of hundreds of interferon-stimulated genes
Viruses may induce an “unfolded protein response” in an infected cell
How does this affect the cell?
Viruses can induce a lot of viral protein synthesis within the host cell. In Eukaryotes, protein over-production results in poor folded proteins in Endoplasmic reticulum in which chaperone are present in a limited ammount. This leads to the “Unfolded protein response” process which can result in either production of more chaperones, or lead the host cell to apoptosis.
How many a virally infected cell defend itself?
Apoptosis - controlled cell death
Autophagy
Cell cycle modulation
IFN production
MHC presentation
Autophagy is a cellular defence mechanism for virally infected cells.
How does it work?
Autophagy is a process by which a portion of cytoplasm is enveloped inside a double-membrane vesicle and shuttled to lysosomes for degradation. It plays both anti-viral and pro-viral roles in the replication cycle of many virus families.
Anti-viral role: viral components are enveloped by autophagy and targeted to degradation through lysosomes, in a process called xenophagy. It would also modulate innate immunity by bringing cytoplasmic viral components to endosomes, thereby activating tool-like receptors innate immunity activation.
Pro-viral role: Some viruses use the autophagy machinery to facilitate their replication or non-lytic cellular egress. This would be the case of many positive stranded RNA viruses which hide their dsRNA replication intermediate into cytoplasmic vesicles. Also some non enveloped viruses like poliovirus may use autophagy to exit the host cell without lysis.
