Negative Strand RNA Viruses Flashcards
What are the non-segmented negative RNA viruses?
Filoviruses paramyxoviruses pneumoviruses Rhabiroviruses Bornaviruses
What are the segmented negative negative RNA viruses?
Bunyaviruses
Orthomyxoviruses
Examples of filoviruses?
Ebola
Marburg viruses
transmitted by fluids
Examples of Pneumoviruses?
Human respiratory syncytial virus
No vaccine
200k deaths per year
Examples of paramyxoviruses?
Measles virus
systemic infection
vaccine but still 500k deaths per year
Examples of rhabdovirus?
Rabies virus
60k deaths
transmitted via dog & bat bites
What are the 3 defining characteristics of neg strand RNA viruses?
1 - genome is non-coding
2 - RNA polymerase
3 - genome is not naked
What is the RNP?
RNA genome covered end-to-end
RNA becomes ordered into helical structure
RNA in RNP is resistant to RNase
How does N bind the RNA genome?
Rhabdovirus N protein & RNA forms rings
N-RNA interacts via phosphate backbone via K & R amino acids
What does RNP structure look like when imaged by cryo-EM?
RNA tightly hidden in a cleft
3 N molecules + RNA
Why is VSV a good model virus?
just 5 genes rapid growth easy to purify very stable not human pathogen
What are the 5 genes of VSV?
Nucleocapsid protein - wraps RNA into RNP helix Phosphoprotein - RdRp cofactor Matrix protein - links N with G Glycoprotein - spikes Large protein - RNApol
what is the mRNA transcription?
neg sense copied into pos sense mRNAs by RdRp
pos sense mRNAs translated on host cell ribosomes
What are the 3 basic stages of VSV transcription?
1 - RdRp binds to genome at 3’ end
2 - RdRp locates at gene start - copies template into pos strand RNA
3 - RdRp responds to signals in genome to stop copying
What are the transcription signals in VSV?
start signal - AACAG
Stop signal - AUACUUUUUUU
gene junctions with both with a space in-between the stop and start
RdRP responds to these signals - one mRNA per gene
What causes the gradient of transcription?
1 - SINGLE 3’ RdRp entry site
2 - RdRp can only move in one direction
3 - RdRp can fall off the template at GENE JUNCTIONS
What are the 3 major DIFFERENCES of RNA replication to transcription?
1 - copying starts at extreme end of the template - RdRp binds at 3’ end & first nucleotide to be copied is position1, in transcription its pos44
2 -RdRp ignores gene junctions in replication - in transcription RdRp stops
3 - New antigene is wrapped in N protein - in transcription the mRNAs are naked
replication occurs AFTER transcription in VSV
How can weak viruses for vaccines be made?
change position of certain genes so they are expressed at a lower level
e.g. Ebola vaccines - N moves to 4th position
