Lecture 4 Flashcards
How do viruses compete with host for translation machinery?
Shut off host translation
-Viruses do not have a cap and use IRES instead
-IRES recruits 40s ribosomal without using eIF4E
-eIF4E gets degraded–>blocks host translation for host while still translating for virus
Between icosahedral and helical capsids which is more likely to assemble without a genome inside?
Icosahedral
-helical capsids require genome
What 2 ways can envelope be acquired and released?
- Sequential
- Concerted
How do enveloped viruses enter and exit cells?
Enter:
1. Fusion
2. Endocytosis
Exit
1. Budding
2. Exocytosis
How do non-enveloped viruses enter and exit cells
Enter:
1. Form a hole–>penetrate membrane
2. Endocytosis
Exit
1. Cell lysis
2. pore forming
3. exosomes
Characteristics of cell intrinsic immunity
-present in ALL cells
-fast to respond
-Hard coded in genome
-detects molecular patterns
Characteristics of cellular innate immunity
-Requires SPECIALIZED CELLS
-Fast to respond
-Hard coded in genome
-Detects molecular patterns
Characteristics of Adaptive immune response
-Requires SPECIALIZED CELLS
-SLOW to respond
-Adapts to pathogens
-detects very SPECIFIC molecular patterns
-Changes/evolves over time–>NOT hard coded
Which immune system cannot adapt to pathogens during infection?
- Cell intrinsic immunity
- Cellular Innate Immunity
Which imune system requires specialized cells?
- Cellular innate immunity
- Adaptive Immunity
True or false: Not all animals have an innate immune system
False
All animals have an innate immune system
What is the key signaling molecule in cell intrinsic immune system
Interferon (IFN)
What triggers the cell intrinsic innate response?
The presence of viral nucleic acid
What is a PAMP
Pathigen Associated Molecular Pattern
-Nucleic acid for viruses
What is PRR?
Pattern recognition receptor
What does the PRR RIG-I recognize?
Short dsRNA
What does the PRR MDA-5 recognize?
Long dsRNA
What does the PRR cGAS recognize?
dsDNA
Where does the dsDNA in the cytoplasm that cGAS recognizes come from?
When mitochondria is under stress by RNA viruses it makes it leak dsDNA
What is the pathway for RIG-I and MDA-5?
- Adaptor: MAVS
- Protein kinase: TBK1
- Transcription factors: IRF3 and IRF7
- Product: Type I IFN alpha and beta
What is the pathway for cGAS?
- Adaptor: STING
- Protein kinase: TBK1
- Transcription factors: IRF3 and IRF7
- Product: Type I IFN alpha and beta
What are ISGs
Interferon stimulated genes
-can singularly block any step in viral infection
How are ISGs made?
IFN will bind to receptor IFNAR which activates protein kinase
-Transcription factors STAT1 and STAT2 are phosphorylated
-translocated into nucleus
-ISGs are made
What is autocrine signaling?
IFN binds to receptors on the SAME cell that made the IFN & activates transcription on that cell
What is paracrine signaling?
IFN binds to receptors on NEIGHBORING cells and activates transcription on those cells
How are uninfected cell be warned & prevent infection?
Paracrine signaling from infected cell
What is an example of a specific ISG and how does it work?
TRIM5alpha–>specific HIV restriction factor
-binds to HIV capsids & forces them to uncoat quickly–>disrupts reverse transcription
How can viruses evolve around TRIM5alpha?
Viruses can change its sequences of their core proteins so TRIM5alpha cannot bind
What is an example of a general ISG and how does it work?
Protein kinase R (PKR)–>general mRNA translation inhibitory factor
-activated by dsRNA
-phosphorylates eIF2alpha–>prevents cap dependent mRNA translation
How can viruses evolve around PKR?
Cap independent mRNA translation
What are the 2 cell death pathways?
- Apoptosis
- Pyroptosis
How does apoptosis work and what signals it?
Cell death is caused by caspases 3 and 7
External signal: TNFalpha
Internal signal: Cell stress (mitochondrial damage)
How does pyroptosis work and what signals it?
Cell death is caused by inflammasome and caspase 1
-IL-1beta and IL-18 causes inflammation and cell death
What can repress gene expression?
Small RNA molecules (siRNAs)
How does RNAi work?
Perfect complementary to target leads to cleavage
-important in plants and eukaryotes
How do microRNAs work?
Imperfect complementarily to target leads to mRNA translation repression
