Viral replication Flashcards
What is the role of the viral envelope and capsid outside the cell?
Protect the virus from extreme conditions
What is the role of the viral envelope and cpasid inside the cell?
Recognises target cell
Protects virus from the innate immune system
What does virus do when it encounters a host cell?
Virus recognises cell and binds to it
Virion disassembly
Genome delivered into cell - directly of taken in and delivered downstream
Genome replication
Gene expression to produce viral proteins
Virion assembly - viral particles are constructed and released
Adjacent cells become infected
What type of replication is viral replication?
Cyclic
How are viruses transmitted?
Aerosols - mucus droplets
Blood - vectors
What are the two challenges to virus entry?
Recognising cell
Crossing the membrane
How do viruses recognise cells?
By identifing cell membrane receptors
If no appropriate receptor on cell - virus won’t infect it
What do cell surface proteins define?
Define the tropism of a cell
If binding of virus onto receptor does not cause viral replication - virus won’t bind to it
What happens when viruses binds to cell surface proteins?
Cell surface proteins activate intrinsic mechanisms in the cell
Regulate replication mechanisms with in the cell
Virus exploits the properties of these proteins
What are the two ways in which viruses enter a host cell?
Virus fuses or penetrates cell membrane
Virus is internalised by endocytosis
What determines the pathway of entry of a virus?
Whether the virus is enveloped or not
Entry of a non-enveloped virus
Structure of virion changes once bound to CSM
Proteins that make up the capsid move relative to each other
Hydrophobic sequence of peptides are exposed
Penetrates the membrane-
produces a pore
Genome is injected
What mechanism of virus entry do non-enveloped viruses use?
Form pores in the CSM
What is a non-enveloped virus that enters the host cell via formation of pores in CSM?
Polio
Entry of an enveloped virus
Viral envelope = lipid
Viral envelope fuses and become continuous part of the cell membrane
Contents of the virion are internalised into endosome
Endosome moves into the cell
Down the veiscular transport pathway
Luminal pH decreases
Release of capsid into the host cell
What protein on viruses bind to CSM of host cells?
Haemagglutinin
What do Haemagglutinin proteins on viral particles bind to on host cells?
Sialic acid
What is an endosome?
Membrane bound compartments
What happens as the endosomes move into the cells?
Endosomes formed by the CSM of the host
Luminal pH decreases
pH of 5.5 - Haemagglutinin complex undergoes conformational change and transition
This causes a thrusting motion
Target membrane and Haemagglutinin fuse
Releases capsid
Basics of gene expression
DNA -> transcribed -> mRNA
By RNA polymerase
mRNA -> translated by ribosomes -> produce proteins
How do viruses replicate?
Use the protein synthesis machinery of host cells
What is the Baltimore classification?
Deduced the relationship between viral genome and mRNA
mRNA = + sense
In order to make proteins, have to make mRNA first
Divides the viruses into 7 classes depending on their DNA sequence
Why do viruses have to make mRNA in order to replicate?
Central dogma
DNA -> mRNA -> proteins
Since viruses have to use the host replication machinery, it has to make mRNA in order to replicate
What sense is mRNA?
Positive stranded
What are the different types of genome in viruses?
Double stranded DNA
Single stranded DNA
Double stranded RNA
Positive single stranded RNA
Negative single stranded RNA
Single stranded RNA reverse transcriptase
Double stranded DNA reverse transcriptase
How do double stranded DNA viruses make viral proteins?
Transcription of the - strand of DNA to form + mRNA
This is then translated to from viral proteins
DNA-dependent DNA polymerase
How do single stranded DNA viruses make viral proteins?
Replicate the single stranded DNA to make double stranded DNA
Transcription of the - strand of DNA to form + mRNA
This is then translated to form viral proteins
How do double stranded RNA viruses make viral proteins?
If you break down the double stranded RNA you have:
Negative stranded RNA
Positive stranded RNA
Positive strand RNA can be used directly as mRNA to form viral protein
Negative strand can be used as a template to make more positive strands
How do single positive stranded RNA viruses make viral proteins?
Could use positive stranded RNA as mRNA
But - have to produce a lot of viruses
So in order to increase viral load:
Positive stranded RNA serve as a template
Form negative stranded RNA template
The negative stranded RNA template forms lots of positive stranded RNA
Some are used as mRNA to make viral proteins and some are used as genetic material
How do single negative stranded RNA viruses make viral proteins?
Use single negative stranded RNA as a template
Produce positive stranded mRNA
RNA-dependent RNA polymerase
When is RNA-dependent RNA polymerase used?
Going from RNA to RNA
When is DNA-dependent RNA polymerase used?
Going from DNA to RNA
How do single stranded RNA reverse transcriptase viruses make viral proteins?
Use single stranded RNA to produce DNA single strand
Use reverse transcriptase enzyme
This is a DNA hybrid - one RNA strand and one DNA strand
RNA strand in double stranded helix can be removed using enzymes
Two DNA strands come together to form double helix
Insert into the genome of the host
DNA-dependent RNA polymerase is used to make mRNA
mRNA is transcribed to make viral proteins
How do double stranded DNA reverse transcriptase viruses make viral proteins?
Start with double stranded DNA
Take a strand of DNA transcribe it to make positive sense RNA
RNA is then reverse transcribed to form double stranded DNA
DNA-dependednt RNA polymerase is used to make mRNA
mRNA is transcribed to make viral proteins
What is the genome of the Herpes simplex virus?
Double-stranded DNA
What is the structure of a Herpes simplex virus?
Contains double-stranded DNA genome
Surrounded by tegument
Tegument contains proteins on its surface (VP16)
What is an important tegument protein?
VP16
Regulates gene expression
Describe process of Herpes virus replication
VP16 on tegument enters host cell
VP16 has a nuclearlocalisation signal and traffics to the nucleus
Binds to DNA promoter sequences
Promoter sequences happen in 5 places of the viral genome
VP16 binds to sequences of DNA and recruits host transcription machinery
Transcription initiates in these 5 genes
What do the 5 genes on the Herpes genome that are transcribed code for?
These genes regulate subsequent gene expression machinery
Early genes express DNA replication machinery
Late genes express structural proteins
What are the bases that code for promoters?
TAATGARAT
What is the genome of the polio virus?
Positive sense RNA virus
Describe the process of viral replication in polio
Virus enters and recruits ribosomes by IRES at 5 prime end of the genome
Ribosome binds directly to the mRNA
Genome is translated
Translation forms 3 large single protein molecules as well as protease
Protease claves polyproteins into smaller units that form:
Part of the virus
RNA polymerase that replicates the genome
Difference between Polyomaviruses and Herpes viruses?
Polymaviruses - recruits host machinery
Herpes virus - encodes polymerase and accessory proteins (polymerase, helicase, primase)
Get same outcome
How are viruses released?
Some bud through membranes automatically - budding
Some kill the cell and release contents via cell lysis
Some bud across the membrane like endosome - exocytosis
What are two ways in which viruses are assembled?
Virus encodes scaffold proteins and particles are assembled around that
Virus factories form bringing proteins together
