Viruses Flashcards
What is a capsid?
Protective protein shell surrounding the genome and forming the core of the viral particle
Why is influenza a respiratory disease?
It contains a lipid envelope which is not very hardy and couldn’t survive passage through organs such as the stomach
How does Rotavirus survive?
It contains a nucleocapsid, inner capsid and outer capsid that makes it very hardy for passage through the gut and is transmitted through the fecal-oral route.
All DNA viruses are…?
icosahedral
All helical RNA viruses have…?
an envelope
What is a common method for detecting viruses?
“Viral gene detection” using PCR, quicker than viral cultivation
What are the stages in viral replication?
1. Attachment/Adsorption
- Virus binds specifically to a receptor on the cell plasma membrane. This defines and limits the host species as well as the type of cell that is infected.
Receptors may be:
- protein (e.g. ICAM-1 for most rhinoviruses)
- carbohydrate (sialic acid for influenza virus)
2. Penetration: 2 ways into a cell
- enveloped viruses may fuse with the host cell membrane and release virus nucleocapsid directly into the cytoplasm
- enveloped and non-eveloped viruses may enter via endocytosis
3. Uncoating
release of the viral genome from its protective capsid
4. Amplification of the viral genome
- DNA viruses replicate mainly in the nucleus and RNA viruses mainly in the cytoplasm. (Exceptions are influenza virus and poxvirus.)
- Early proteins = non-structural (eg. DNA or RNA polymerases)
- late proteins = structural, eg. capsid proteins, ie. building blocks of the virion.
5. & 6. Assembly and Release
Non eveloped viruses: spontaneous assembly of the capsid proteins around the nucleic acid genome. Virions accumulate in the cytoplasm or nucleus andreleased when cell lyses.
Enveloped viruses: release by budding from the cell surface. Capsid proteins and nucleic acid condense directly adjacent to the cell membrane and bud off.
How do + and - sense RNA viruses and DNA viruses replicate?
+ sense RNA viruses
need to translate non structural proteins such as RNA dependent RNA polymerase enzymes via ‘Autocleavage’ before they can synthesise new - and + sense mRNA.
- sense RNA viruses
need to carry in their RNA dependent RNA polymerase with them into the cell it infects
DNA viruses
use the host cell DNA dependent RNA polymerase to replicate their genome
What are the virus induced changes in cells?
Inclusion bodies- represent accumulated viral proteins at the site of virus assembly i.e. ‘virus assembly factories’
Cell transformation- Some viruses encode oncogenes whose expression code for proteins with growth promoting properties and can lead to uncontrolled proliferation of the infected cell and tumour development
How do viral genomes change?
How can viral infection be halted?
How do viruses enter via the respiratory tract?
- most important site of entry
- acquired by aerosol inhalation or mechanical transmission of infected nasal secretions
- droplet size determines initial site of virus deposition: >10um lodge in nose; 5-10um airways; <5um alveoli of lower respiratory tract
**barriers to infection: **mucus, cilia, alveolar macrophages, temperature gradient, IgA
- viruses attach to specific receptors on epithelial cells
- can remain localised eg. rhinovirus or spread further eg. measles, mumps, rubella
How do viruses enter via the alimentary tract?
- Viruses that infect the intestinal tract are normally acid and bile resistant and don’t have an envelope (because lipids in the envelope can be broken down)
- Some viruses cause diarrhoea, eg. rotavirus
- Others do not cause disease in the intestinal tract but spread from there to cause systemic infection, eg.poliovirus, hep A virus
- If viruses do not have receptors for epithelial cells need to enter via a breach in the epithelial surface eg. HIV, Hep B can infect via abrasions of the rectal route
What is an example of a local infection?
**Intestinal tract: local infection **
- Rotaviruses have a triple-shelled capsid
- Infect and destroy epithelial cells of the intestinal villi and M cells causing inflammation and diarrhea (gastroenteritis); dangerous in infants
What is the typical course of viraemia?
What is an example of a systemic infection?
What are the determinants of tropism?
How do some viruses suppress the immune system and what is the outcome?
Immunosuppression
eg. HIV: replicates in CD4 T cells and kills them and in monocytes and inhibits their function
eg. measles: temporary immunosuppression from nonproductive replication in T cells and macrophages; suppression of proliferation of non-infected T cells by infected DC displaying measles surface glycoproteins; suppression of IL-12
– leads to susceptibility to secondary infections
What are some strategies viruses use to evade the immune response?
1. Antigenic variation
change in structure of binding site where neutalising Ab would normally bind to escape neutralisation
e.g. HIV (drift in a single patient)
Influenza (drift at a population level)
2. Inhibit T cell priming by DC
inhibition of DC maturation so T cell help is not recruited
e.g. Vaccinia (produce TLR homolog where Ag would normally bind to inhibit signal transduction)
HSV block signal transduction in DC
Vaccinia, HCV block DC maturation
Measles, CMV block T cell stimulation
3. Evasion of CD8 T cell recognition
avoid CD8 T cell recognition to reduce cytotoxic killing of infected cell
e.g. EBV inhibits proteosome
HSV, CMV bind and block TAP
Adenovirus anchors MHC + peptide to ER (prevent presentation on the surface)
HIV - antigenic variation in epitope and endocytosis of MHC I if presented (i.e. different or transient target for CD8 T cells)
How is NK cell killing mediated and how do viruses avoid it?
e. g. 1. Murine CMV retains NKG2D ligand in ER (i.e. no activation receptor stimulation on NK cell)
e. g. 2. Human CMV encodes MHC class I-like molecule that delivers negative signal to NK cell (i.e trick NK cell to inhibit killing)
What is a mechanism interferons use to prevent viral spread and how do viruses overcome it?
What are the genetic factors influencing susceptibility to viral infections?
inherited defects eg. absence of Ig class
polymorphisms in genes controlling immune responses eg. MHC genes (certain virus Ag are much better presented on some MHC molecules)
interferon-inducible genes (MxA and MxB) (specifically interfere with the influenza replication cycle)
receptor genes eg. CCR5 (HIV co-receptor, lack of receptor has HIV resistance)
What are the physiological factors that influence susceptibility to viral infections?
age - newborns and elderly are more susceptible to severe disease (immature immune response) but young suffer less from immunopathology (less immunoreactivity)
malnutrition - decreases resistance hormones, pregnancy - males and pregnant women more susceptible
dual infections - may result in more severe disease
