Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
23 Cards in this Set
- Front
- Back
|
What is IRES and what does it do? How is it related to vaccines?
|
IRES (internal ribosome entry site) is in the 5' UTR in polio (and other viruses). It has a highly conserved secondary structure with 6 hairpin loops (a mutation in loop four is what causes attenuation in the sabin virus). At the end it contains an AUG.
It binds directly to the 40s ribosome and places AUG in the correct place for initiation. To do this is requires extra cofactors (to stabilise it-they "open up the structure of the RNA to allow the virus in). It requires fewer initiation factors (doesn't need eIF4E which is cleaved by a protease). It therefore has a competitive advantage over normal cellular transcription. |
|
|
What are the two types of polio vaccine, how are they made and and what are there advantages/disadvantages
|
Sabin-Attenuated virus made by serial passages through cell lines so that the virus becomes lazy. It can be orally delivered, is cheap and has some replication in the intestine (better immunity). Can pass person to person so you can get heard immunity. But a reversion can occur
Salk-A dead virus. Inactivated by treating with formaldehyde (binds the RNA to the capsid). There is no risk of infection or reversion but it is expensive, need to be injected and can be injected live (cutter incidence). |
|
|
What is RSV
|
RSV=Ralph sarcoma virus from chickens. It contains an incomplete src gene which codes for a tyrosine kinase. The phosphorylation site is gone (how it is normally inactivated) so it is always on. This causes breakdown of the extracellular matrix and cancer.
|
|
|
What is HaMLV?
|
MLV with a ras gene. Upon growth factor binding RasGDP turns to RasGTP and activates many genes. The over expression here leads to cancer
|
|
|
MMT
|
MMT=Mouse Mammary Tumour Virus. This inserts upstream of the oncogene int-1 and enhancer activates it.
|
|
|
Pappillomavirus
|
A DNA virus which normally exists as an episome in the nucleus. However, it can occasionally and accidentally integrate into our genome. When this happens the genes E5 (destabilises the CM) E6 (degrades p53) and E7 are over expressed resulting in cancer.
|
|
|
Scrapie
|
A prion virus from sheep, non infectious to humans. causes dead patches in the brain
|
|
|
Kuru
|
A human prion disease found in papa new guinea. Incubation time was around 4-20 years! most likely stared with one case but spread due to eating of brains.
|
|
|
CJD
|
Creutzfeld-jacob diesase is a human prion disease. incubation time is from 30-50 years. Initally it causes confusion and memory impairment before loss of co-ordination and death
|
|
|
What is GSS?
|
A human prion disease that coours at around 50years. Non-infectious but occurs in families. Results in unsteady gait before death
|
|
|
What is FFI?
|
FFI=familial fatal insomnia is a human prion disease contracted ~40-50 years. It causes mild and then more severe insomnia.
|
|
|
What is PrPc?
|
Prion protein is a membrane bound protein that is involved in regulating CU2+ in brain neurones and other cells. A random mutation can cause it to form a very protease resistant and insoluble PrP* which is autocatalytic for its own formation.
|
|
|
What is INF-alpha how is it induced and what action does it have?
|
INF is an interferon. It is induced by foreign cells, infected cells (virus and bacteria) and cancer.
Along with INF-Beta, it has three main functions: 1) Resistance to viral replication in all cells by attacking multiple stages in the viral lifecyle (SOS state) e.g Translation inhibitory protein (TIP) binds to a pre-existing ribosome and induces extra mRNA checks (viruses have evolved ways around this (cap snatching)) 2)increase MHC1 expression and antigen presentation in all cells 3) Activate NK cells to kill virally infected cells (increases expression by 50-100 fold) |
|
|
What is INF-Beta, what induces it and what action does it have in the body?
|
Induced by viral and other foreign nucleic acids in the boy (e.g dsDNA). It is thought to be derived from a duplication event from INF-alpha.
Along with INF-alpha, it has three main functions: 1) Resistance to viral replication in all cells by attacking multiple stages in the viral lifecyle (SOS state) e.g Translation inhibitory protein (TIP) binds to a pre-existing ribosome and induces extra mRNA checks (viruses have evolved ways around this (cap snatching)) 2)increase MHC1 expression and antigen presentation in all cells 3) Activate NK cells to kill virally infected cells (increases expression by 50-100 fold) |
|
|
Describe Haemagglutinin synthesis.
|
~500 copies per virulon
Synthesis HA is synthesis using the host machinery, completely independent of the virus A precursor is synthesised (HA0) It has a hydrophobic tail which is extruded into the ER. Undergoes modification in the golgi (glycosylation and palmitoyltion) Cleavage occurs by host enzyme (clara) into HA1 and HA2 upon viral release. This is required for activation of fusion abilities. Timing is essential to prevent premature activation. Ha1 and HA2 remain associated by non-covalent interactions and a S=S. After cleavage the N-terminus of HA2 (hydrophobic) refolds into the stem structure (conformational change!!) This is the fusion peptide and it is hidden from the host’s immune |
|
|
Describe cell attachment by ham agglutinin.
|
Binds the cell surface receptor (determines the tissue tropism of the virus e.g. Between birds and humans)
Homotrimer Receptor binding pockets are located at the top (there are three sites per trimer, so 1500/virulon) Possibly in a slight canyon-hard to tell! Binds to the motif, sailic acid (this is the terminal group in the carbohydrate chain in glycoproteins/glycolipids (this is prevalent in many tissues). Human receptor= α2,6 linkage Bird receptor= α2,3 linkage Pigs may have both!!!! After binding the particle is drawn into the cell (there is NO conf change) |
|
|
Describe how hameagluttinin and M2 change in the cell endosome.
|
Promotes pH dependent fusion of viral and cell membranes during entry.
Proton pumps in the endosomal pump H+ into the compartment and so lower the pH Acidification causes a dramatic conformational change in the HA protein The hydrophobic fusion peptide is drawn from the centre of the HA molecule and plunged into the endosomal membrane The virion M2 ion channel (homotetramer) lets H+ into the virulon which releases RNPs from the M1 protein shell (this is why cleavage is left to the end). There is fusion of the viral and endosomal membrane and the RNPs are released (with the polymerase). |
|
|
Describe cap snatching in influenza.
|
mRNA must first be created due to the viral genome being (-)
RNPs: the viral polymerase complex contains PB1 (polymerase), PB2 (Recognizes the cap) and PA (unknown role) Replicates in the nucleus, the polymerase subunit has a NLS (unusual) “Cap-Snatching” Stealing primers from the 5’ end of host mRNA: 1) PB2 binds to the cap and cleaves after the CA 2) U at 3'bp with A in the snatched primer. 3) Bp between the 5' and 3' end of the vRNA (more stable) 4)GTP bp with the 3' end of the template and transcription begins. |
|
|
Describe how the influenza mRNA is polyadenylated.
|
Required for efficient translation and mRNA stability
There is a poly U sequence in the template and stuttering on this generates a poly A tail NOT FRAMESHIFTING (seen in other viruses) Viral mRNA is not an exact copy-the extreme 3’ end of the viral genome is lost. |
|
|
Describe the action of Neruaminidase.
|
Neruaminidase (NA) is homotetrameric removes sailic acid from the surface of an infected cell and virons.
Prevents re-infection and viral aggregation. Target for antiviral drugs (tamiflu). Active as soon as it reaches the plasma membrane. |
|
|
Describe the general mechanisms of oncogene capture.
|
This process is known as acute transformation:
1)The virus is integrated upstream of an oncogene. 2)The 3' LTR is damaged during integration so the oncogene will be transcribed along with the viral genome. INTRONS WILL BE REMOVED. 4) Retroviuses are diploid so non-homologous recombination can occur between the strands during replication (the polymerase will just jump between them). |
|
|
Describe the action of Neruaminidase.
|
Neruaminidase (NA) is homotetrameric removes sailic acid from the surface of an infected cell and virons.
Prevents re-infection and viral aggregation. Target for antiviral drugs (tamiflu). Active as soon as it reaches the plasma membrane. |
|
|
Describe the general mechanisms of oncogene capture.
|
This process is known as acute transformation:
1)The virus is integrated upstream of an oncogene. 2)The 3' LTR is damaged during integration so the oncogene will be transcribed along with the viral genome. INTRONS WILL BE REMOVED. 4) Retroviuses are diploid so non-homologous recombination can occur between the strands during replication (the polymerase will just jump between them). |
