Paramyxoviruses Flashcards
“Para”
Other, next to
“Myxa”
Mucus
What type of genome?
nonsegmented (-)ssRNA
What type of structure?
Helical nucleocapsid with a pleomorphic envelope
Rinderpest morbillivirus
Cattle plague with almost 100% fatality
Eradicated in 2011 by vaccines
Morbilivirus
Italian for “little disease” because big disease was The Plague
Where did measles come from?
Zoonotic transmission from rinderpest virus. Couldn’t have existed until about 5000 years ago because that’s when we had large enough civilizations to feed it
What is the VAP?
Hemagglutinin
What is used for membrane fusion?
A fusion protein (F)
Does measles have Neuraminidase?
No
Nucleoprotein (N)
Coats the RNA genome
Large protein (L)
The RNA dependent RNAP
Phosphoprotein (P)
A cofactor needed for RNAP and to attach the nucleoprotein to the genome
Life cycle
- Attachment - Hemagglutinin binds host SLAM
- Penetration/entry - fusion protein (F) fuses plasma membranes
- Uncoating
- Gene expression - mRNA synthesis using viral RNAP in the cytoplasm (P and L)
- Genome replication - in the cytoplasm (N, P, and L)
- Assembly - at plasma membrane (N, P, and L)
- Release - via budding
How is the lifecycle different from orthomyxoviruses?
Replication occurs in the cytoplasm NOT the nucleus
mRNA synthesis uses which proteins?
P and L
Genome replication uses which proteins?
N, P, L
How does the virus know if a mRNA is used for genome replication or secondary transcription?
Genome replication has N, P, L
Secondary transcription has P, L
N means No stay
How are (-)ssRNA genes expressed?
Viral RNAP converts (-)ssRNA to (+)ssRNA
Host translates (+)ssRNA (mRNA)
Some new (+)ssRNA is converted back to (-)ssRNA for genome replication
Transcriptional polarity
3’ genes are transcribed more efficiently than 5’ genes because of polymerase skipping at polyU sequences between genes
What is the first gene transcribed and why?
Nucleocapsid because need many copies of subunit
What is the last gene transcribed and why?
L (the viral RNAP) because it can process many (-)ssRNA
How is measles transmitted?
Respiratory aerosols
Fomites - contaminated object or surface
What is a fomite?
A contaminated object or surface
What is measles known for?
Being the most contagious human virus. One infected person infects on average 12-18 others
What is needed to maintain measles?
A population size of 500,000 (16,000 newborns a year)
Why do Guam and Bermuda have such high incidences of measles?
Goddamn tourists
Primary site of replication?
Regional lymphoid tissues (macrophages and dendritic cells)
Secondary sites of replication and how does it get there?
Dendritic cells carry it to T cells, B cells, and epithelial cells
What is the receptor for primary replication?
SLAM
What is the receptor for secondary replication?
Nectin-4 (epithelial cells)
Common symptoms of measles
High fever
Red watery eyes
Bronchopneumonia
Congestion/Runny nose/Cough
Transient immunosuppression
Skin rash
Rare symptoms of measles
Encephalitis
Subacute sclerosing panencephalitis (7-10 years after infection)
Death
When are you infectious and why?
After a week because that’s when it can escape epithelial cells
Immune amnesia
Severe but transient immunosuppression
Severe depletion of T cells and B cells = lose memory cells
When does the body recover from immune amnesia?
36 months
Measles live-attenuated vaccine (John Enders)
Many passages in human cells to create host range mutations because we are the only known host
Many passages in chicken cells to attenuate by host range mutations and temperature mutations
Henipaviruses
Paramyxoviruses of zoonotic concern (Hendra virus and Nipah virus)
From bats