Pathogens 3 - Viral infections Flashcards
What are the 3 ways a virus is classified?
-type of nucleic acids used for genomes
- their physical shape
- if they have an envelope
The cell membrane is a barrier to the entry of viruses. What are the 3 ways a virus can enter?
What 2 things does a virus need to do to make more virus?
- Make more viral proteins
- Copy their genomes
How do DNA virus make more viral proteins and copy their genome?
How do RNA virus make more viral proteins and copy their genome?
Once inside a cell the virus must create new copies of itself. How does it do this?
Give 2 characteristics of new viral particles?
-Wholly self assembling
-no energy input to exit
The cell membrane is a barrier for the exit of newly formed viruses? Give 3 ways they can leave?
What kind of virus is influenza?
What are the 3 types of influenza virus?
- Enveloped –ssRNA viruses with a segmented genome
- A, B and C (only A causes pandemic disease - jumps between spieces)
What is the viral RNA polymerase?
What are the 2 main important proteins encoded on influenza that cause attachment to and exit from cells?
- Replicase (the viral RNA polymerase)
- Haemagglutinin
- Neuraminidase
What are the 2 parts of the respiratory tract? What is the difference between them in terms of defence?
- mucociliary escalator
-The conducting airway reaches down as far as the terminal bronchioles
How do we investigate pathologies in airway infections?
-X-rays
What are the 3 phases of the immune response to influenza?
1) Cytotoxic
2) Neutralising
3) Suppressive:
-Time for the repair of the ciliated epithelium.
-The strength of the TH2 response also suppresses TH1 and TH17 responses for weeks afterwards. >susceptible to bacterial respiratory infections
How does Influenza infects epithelial cells by binding sialic acid with haemagglutinin and causing clathrin-mediated endocytosis?
-haemagglutinin = adhesin
-Sialic acid = attachment molecule
Influenza viruses have a genome made of negative-sense RNA , what must happen? (Early infection)
- Copied into positive- sense RNA if they are to works as mRNA and make proteins.
»YOUR CELLS CANNOT COPY RNA TO RNA
»>The virus brings a premade protein known as replicase with them to function as an RNA- dependent RNA polymerase. - This copies negative-sense to positive-sense RNA.
- These positive-sense segments function as mRNA and can now trick the ribosomes into making viral proteins for genome and virulence factors
Once the genome amplification is well under way, What do the late genes stimulate?
-drive synthesis of the haemagglutinin and neuraminidase
- needed to form the viral envelope and for subsequent exit from the cell.
Haemagglutinin on the surface will stick to the sialic acids again, resulting in an inability to leave the surface of the cell! Viruses hanging around on the surface of cells will attract complement and result in swift destruction… How do virus avoid this?
-Neuraminidase
Thinking immunologically wise what does viral infection result in?
How does influenza contradict this?
-TLR 3/7+RLR detect dsRNA : cause Type 1 interferon release
-RAPID INCREASE IN INTERFERON ALPHA LEVELS. This should lead to recruitment of NK cells and killing of the infected epithelial cells
-IFN B: Activate further expression of IFNα in local cells, Reduce protein synthesis, slowing viral replication
-Slow down the rate at which IFN-alpha is produced. This subsequently slows down the likelihood of its host cell being killed off by NK cells and increase its chances of making it to viral release
Early infections cause upper airway damage, what does this result in?
-Release of DAMPs.
>These result in the beginnings of inflammation and the first symptoms…
- Mucus production in the upper airway can begin and the patient will cough and sneeze due to irritation.
>Blasts the droplets containing new virus into the environment.
As the virus sheds it can move down and infect cells in the lower tract… What happens?
-neutrophils/nk cells will begin to infiltrate in modest numbers. >The continued loss of ciliated epithelium in the upper tract makes it harder to remove the debris and contributes to the cough
How do we massively reduces the viral load and prevent a large proportion of the viral replication.
- DC take presented antigen, on MHC-II, to the T-helper cells
> Huge amount of type-I IFN and viral RNA knocking about, so the DC will be driven to make as much IL12 as possible. (Th1) - Lots of Viral RNA> cross- presentation and allows DC to activate cytotoxic T-cells as well.
–The key here is that a DC presenting antigen to a T-helper cell (on MHC-II) also has a cytotoxic T-cell recognising antigen on an MHC-I can be given enough IL2 from the activating TH1 cell to begin to proliferate. - T-cell response returning to the tissue kills a lot of the infected cells. Huge numbers of lung epithelial cells are destroyed and the patient feels very unwell
TH1 responses reduce number of viruses being produced, but antibodies needed to ensure lasting immunity. How?
- The amounts of type-I interferons and vRNA will go down.
> Biggest signals the DC will get is from the viral particles it captures while they are trying to escape or reinfect.
> These have H and N proteins, which are huge triggers for IL4 synthesis in DCs. - Any DC presenting antigen to TH0 cells will now result in TH2 polarisation and lead, inevitably to plasma cell generation and antibody production against H and N proteins.
- The virus cannot reinfect and the TH1 response is suppressed
Why do we get the flu every year?
-ANTIGENIC DRIFT- mutations at random points in the H and N RNA sequence give rise to new surface antigens
How is a pandemic influenza caused?
-Human influenza A virus enters an animal cell that has already been infected with another influenza virus > no way for the cell or the viruses to know which RNA segments belong to which virus.
-Segments 1,2,3,5,7&8 have to come from a human influenza infection to defeat human immune system…. Neuraminidase and haemagglutinin of porcine and avian influenza viruses work just fine on human cells though.
- So… you could get an influenza A virus that has human-derived segments required for completing an infective cycle but had a porcine-derived H and N on their 4&6 segments.
> No human will ever have produced antibodies against these
Summarise the general viral life cycle.
