Measles Flashcards
Where does measles virus enter and replicate?
- enters respiratory airways
- first infects myeloid immune cells
- then infects lymphocytes via CD150 receptors and replicated in their cytplasm
How can measles virus spread between cells without budding?
- facilitated by actin rings or through pores between cells
- leads to infection of epithelial cells in the respiratory tract to allow for transmission via coughing
Describe the genome of a paramyxovirus such as measles
- 2 NTRs 3’ leader and 5’ trailer
- 6 ORFs
- nucleoprotein, phosphoprotein, matrix, fusion protein, HA/M proteins and polymerase
- phoshoprotein can be in 3 isotypes P, C or V
- transcripts at the 3’ end are more abundant than the 5’ end
What is the role of a virus nucleoprotein?
associates with the virla genome and facilitates transcription
What is the role of a virus matrix protein?
assembly and budding
What is the role of a virus phosphoprotein?
facilitates genome replication and immune evasion
How does the measles virus phosphoprotein have 3 isoforms?
- normal initiation forms P
- often the ribosome misses the start codon and begins at a later one to form C
- other times an extra G is added into the mRNA in transcription changing the reading frame to form V
How do the measles phosphoproteins affect the innate immune response?
- P+V prevent phosphorylation of TF STAT1
- C + P counteract interferon induction in infected cells
What are some ways in which phosphoproteins affect innate responses in more deatil? (4)
- inhibit RIG-1 activation
- sequesters NFkB subunit RelA and keeps it in the cytoplasm to inhibit signalling
- repress IFN-B transcription in the nucleus
- negatively regulate PKR
describe measles infection
- blotchy rash spreading from the face and skin sloughing
- extremely infectious
- infection produces life long immunity
- life long immunity means that small communities can’t sustiain infection so it was likelt a zoonotic infection until our populations become large enough
How long does measles last and what can the complications be?
- children up to 10 days adults longer
- can cause meningitis, encephilitis, bronchitis and death
Why does measles infect and kill so many people?
- has an extremely high H0 meaning very few particles are required to cause infection
- millions of lives have been saved by the MMR vaccine but measles is resurging globally
How can measles enter a host?
- through the respiratory epithluim by droplets or through the conjunctiva of the eye
- infects DCs or alveolar macrophages that travel to lymphoid tissue where the virus can spread to CD150+ lymphocytes
How does systemic dissemination of measles occur after infection of lymphocytes?
- lymphocytes enter the blood and migrate to other tissues and organs
- infection can deplete CD150+ lymphocytes and cause usually temporary immunosuppression
- T cells can infiltrate the skin and clear infected cells resulting in the rash
How, following viraemia, do measles viruses infect epithelial cells when they are CD150 negative?
switches to use Nectin-4 in the basolateral surface of airway epithelium
How is the measles vaccine made?
- serial passage in cell culture
- initially grown in kidney cells now in chick embryo fibroblasts
- one of the safest and most effective vaccines ever made
How does the measles vaccine work?
- molecular basis is unclear
- most of the mutations just contribute to its attenuation
- altered H protein sequence makes it use CD46 to attach and enter cells
- this is expressed on many cell types but the vaccine strain still chooses to use dendritic cells
What is the link between measles and cancer?
- reports of infection with measles virus causing regression of tumours
- attenuated measles uses CD45 which is upregulated in cancer
- promising phase 1 trials against T cell lymphoma using the vaccine strain
- nectin 4 is also upregulated in some tumours
Why might the measles virus vaccine be goof for other virus vaccines?
- can be used as a delivery system for other viral proteins by inserting other genes into the backbone
- used for Chikungunya even in those previously vaccinated against measles
What is mumps?
- paramyxovirus like measles
- causes swollen salivary glands and can have CNS involvement such as meningitis
- can also cause temporary or premenant deafness
What kind of genome does a paramyxovirus have?
ss negative sense
What is Rubella?
- rubivirus positive ssRNA virus
- very effective vaccine makes rubella rarely seen
- can cause babies to be born with congenital rubella syndrome causing deafness, blindness, brain damage etc
What kinds of reasons may people be hesitant to vaccination?
- internet and social media
- misinformation and distrust
- culture and religion
- safety concerns and lack of knowlege
How are MMR primarily transmitted?
through respiratory droplets
What is the MMR vaccine>
- live attenuated vaccine that is very effective
- disinformation and resistance have impaired efforts to eradicate the viruses especially measles
- e.g. autism paper
