Calcivirus Flashcards
What are calciviruses?
- positive sense ssRNA viruses
- major cause of non-bacterial gastoenteritis
- causes 50% of outbreaks in the UK
- 4 family members of which norovirus and sapovirus infect humans
What are the main symptoms of calciviruses?
- vomiting (more in norovirus)
- diarrhoea (more in sapovirus)
Why does calcivirus spread so easily?
- recover quickly symptomatically but still shedding lots of virus
- very infectious
- hard to kill in the environment
Describe the virus particle of calcivirus
- minor capsid protein encloses the RNA genome
- surrounded by a major coat protein
How does calcivirus genome replicate?
- like most positive sense RNA genomes
- genome gets translated to form viral proteins that are used in assembly or replication
- negative sense RNA strand is formed by the polymerase which is then made to synthesise progeny genomes for packaging
Describe the calcivirus genome
- plyadeanylated at one end
- ORF1 - non structural proteins
- ORF2 - major structural proteins
- ORF3 - involved in assembly
Describe the basic lifecycle of calcviruses
- entry is poorly understood
- genome is translated and cleaved to form the viral polymerase and other viral proteins
- polymerase makes the antigenome from which subgenomicRNA is made
- accumulation of the major capsid protein occurs and the particle is assumed to self assemble as expression of major capsid protein causes virus like particles in culture
What is the vpg protein of calcivirus?
- ORF1 protein key to feline-calcivirus translation
- covalently attached to the 5’ end by a tyrosine residue
- interacts with translation initiation factors to enhance translation of the viral genome
How does calcivirus bias host translation towards viral proteins?
- triggers the cleavage of other translation initiation factors
- leads to the shut off of host mRNA translation
- genome contains an IRES that can allow ribosomes to bind in an alternative way
- this shut off also inhibits the expression of interferon-stimulated genes (innate immune response)
The ends of many positive sense RNA viruses are thought to play a critical role in viral RNA replication. Why?
- the ends of viral RNA interact with eachother and with cellular proteins to facilitate replication
- viral RNA appears to need to form a circular molecule for efficient replication
What has been proposed as a potential calcivirus antiviral drug?
- doesn’t target viral proteins
- targets human HSP90 protein that interacts with viral vpg and RNA
- targeting host proteins will slow drug resistance
Why is calcivirus hard to study?
- no good culture method until recently
- still complicated method
- cultured in stem-cell-derived human enteroids with the presence of human bile
What are the primary cellular receptors for attachment of calciviruses?
- histo blood group antigens A, B + H
- variation in viral genotypes and in blood group antigens explains why some are more affected by infection than others
- some people’s blood group antigens don’t interact with the virus as well
How does norovirus enter the cell?
- binds histo blood group antigens and an unknown secondary receptor
- enables virus uncoating and entry by endocytosis
What are histo-blood group antigens?
sugars found on the surface of red blood cells (HBGA)
