Microbiology Flashcards
What is a virus?
Viruses are obligate intracellular parasites that use cell machinery to create more viral components and genomes.
What are the benefits of a DNA genome over a RNA one for a virus?
DNA genomes are more stable, less error prone and can therefore be more complex than RNA genomes. They can even have accessory genes which allow them to evade the immune response.
How long can a RNA virus be?
30 base pairs
Which family of viruses tend to be large DNA viruses?
Large DNA viruses such as Herpesviruses tend to cause latent infection by surviving in the host for a long period of time. To do this they need to interact intricately with the host immune response to avoid detected.
List the popular members of the Herpes virus family
Members of the Herpesviridae include:
- Varicella zoster virus
- Epstein-Barr virus
- Cytomegalovirus
- Herpes Simplex Viruses.
These are extremely widespread amongst humans.
What is required in order to activate the innate immune system against a virus?
In order for a pathogen to initiate any type of response, be it innate (which then leads to adaptive), it needs to activate PRRs (Pathogen Recognition Receptors). After PAMPs (Pathogen Associated Molecular Patterns) bind to PRRs, they can transduce a signal with a cascade of events to mount an immune response.
Give examples of PRRs
PPRs can be cytoplasmic like RIG-I like receptors (RLRs) or on the cell surface like Toll-like receptors (TLRs).
How can PRRs detect viral DNA?
They don’t have a 5’ cap nor 3’ poly-A tail.
What are interferons?
Interferons are soluble cytokines which comprise our innate immunity against viruses (as well as physical barriers).
What are type 1 interferons, and what cells secrete them?
Type 1 interferons are secreted from all infected cells, these include IFN-α and IFN-β.
What are the three major functions of type 1 interferons?
- Induce antimicrobial state in infected and neighbouring cells.
- Modulate innate response to promote antigen presentation and activate natural killer (NK) cells.
- Activate the adaptive immune response
How many isotypes of INF-a and INF-b do we have
While there is only one gene for INF-β, there are 13/14 isotypes of INF-α.
What are type 2 interferons, and what cells secrete them?
Type 2 interferons are produced by activated T-cells and NK cells. IFN-y is the only type 2 interferon
What are the main interferon receptors?
- INFAR (for INF-a and INF-b)
- INFGR (for INF-y)
What molecules respond to type-3 interferons?
Type 3 interferons are a group of INF-λ molecules, whose receptors are mainly present on epithelial surfaces.
Explain how type I interferon synthesis is regulated
- Signalling from RIG-1 or TLR (after the detection of viral RNA) is passed through Mavs (Mitochondiral activation of viral signalling).
- This leads to the nuclear entry of various factors which bind to the promoter region of the IFN-β gene.
Complete the sentence:
- The IFN-β molecule can act through autocrine signalling or paracrine signalling to activate de novo transcription of hundreds of _________.
Interferon Stimulated Genes (ISGs)
How does viral DNA activate signalling in a similar way RNA does through RIG-1?
foreign DNA can be detected through cGAS. cGAS biochemically modifies bits of DNA so that it can be detected by STING on ER to switch on IFN in the same way as RIG-I does.
Outline the canonical type I interferon signalling pathway.
INFa/b binds to a transmembrane INF receptor (INFAR) which heterodimerises [INFAR1 and INFAR2]. Through a series of series of phosphorylation events Tyk2 and Jak1 phosphorylate each other, as well as other proteins in the cytoplasm such as STAT proteins.
The STAT proteins enter the nucleus and bind to the promoter regions of ISGs. These promoter regions are called the Interferon Stimulated Response Elements
Why can the IFN response only be maintained for several hours?
The interferon stimulated genes (ISGs) have a drastuc effect on the cell and can’t be left switched on.
List some important ISGs
- Mx
- PKR
- IFITM3
- APOBECs
Explain the mechanisms of action of IFITM3
IFITM3 (Interferon Induced TransMembrane Protein 3) is an important protein transcribed by a ISG. It inhibits entry of enveloped viruses (such as influenza) which enter the cell via endosomes.
Explain the mechanisms of action of Mx
Mx is a GTPase that can form multimers which wrap around the nucleocapsids of incoming viruses – therefore nullifying incoming virus genomes.
Which viruses are particularly prone to Mx1 and Mx2?
Mx1 inhibits influenza and Mx2 inhibits HIV