Week 3 - Microbiology Viral Replication Flashcards
What are viral pathogens classified by?
Basis of virion structure, characteristics of nucleic acid, and replication strategy
What are viruses?
Obligate Intracellular parasites… must have host cell - if they don’t multiply they will not cause disease
Do viruses produce toxins?
NO. They must multiply to cause disease.
Why vaccinate?
Provide as many antiviral compounds so when virus enters body they do not multiply
Virion
Invections virus particle, what invades the body
What does a virion contain?
Nucleic acid genetic material surrouned by protein coat (capsid)
Some have lipid and glycoprotein envelope
Genomes can be?
DNA or RNA
Single stranded or double stranded
Can have same (+) polarity or complimentary (-) polarity as viral m-RNA
Circular or linear (some segmented)
Positive polarity in viral genomes
Same polarity as viral mRNA (+)
Negative polarity in viral genomes
It is complementary to viral mRNA
Viral genomes are haploid except for what?
Retroviruses.. They are diploid
DNA vs RNA virus genomes
DNA are single stranded, double stranded, or circular
RNA is Single stranded (polarity), segmented or double stranded segmented
Capsids/Nucleocapsids
Nucleocapsid if enveloped
They are composed of many copies of one or very few viral-encoated protein subunits
Their function is in packaging the nucleic acid in viral assembly and protection of the nucleic acid
Capsid Shape
Either cylindrical (helical form) or cubic shape (icosahedron from)
Viral attachment protein (VAP)
Capsids of naked viruses contain VAPs. They are used this to get into other cells
VAPs as drug targets
If an antibody targets and destruct the VAP the virus cant get into cell and cant replicate
Capsomer arrangement
Penton capsomer (surrounded by 5 capsomers) Hexon capsomer (surrounded by 6 capsomers)
Do all capsids contain enzymes?
No. Only some.
Glycoproteins on Nucleocapsids
Specific glycoproteins act as VAPs for enveloped helical nucleocapsids
What is the Envelope composed of?
Lipds, proteins and glycoproteins
The glycoproteins are acquired from viral modified cellular membranes during egress of virus from host cell
What is the viral envelope disrupted by?
Non-moist environments, heat, acid, and lipids solvents…
What is a Peplomer
A glycoprotein
Enveloped helical
Capsomere surrounds nucleic acid in helix form
How are viruses classified?
Nucleic acid, virion structure, replication strategy
How many families of viruses in human pathogens?
21 families, 7 families contain DNA. Viruses in same family don’t always produce same diesease.. Also different families can produce same disease…
DNA viruses
…viridae
Parvo Papo Adeno Herpes Hepadna Pox
RNA viruses
…viridae
Toga Flavi Picorna Corona Paramyxo Reo Bunya Arena Orthomyxo Rhabdo Retro
If viruses don’t multiply they…
…don’t cause disease!*
Obligate intracellular parasite
Use host machinery to produce mRNA so cant target host machinery as drug target… So must find a certain characteristic… to target
What does host range for viruses depend on?
If a virus can…
Enter a cell
Find appropriate cellular machinery
Exit the cell
Productive infections?
Virus infections that yield new infections viruses
Non-productive?
Virus infections occur when the vira genetic material persists in a cell (latent state) but no infections virus is formed
Some _________ infections can lead to oncogenic transformation of cells?
Non-productive
Phases of viral multiplication?
Attachment Penetration Uncoating Virus Component Synthesis Assembly Release
What happens to host cell during synthis of viral proteins?
They often result in morphological changes to the host cell. Called cytopathic effects (CPE)
Cytopathic effets (CPE)
Morphological changes to a host cell that is infected with a virus
What do antivirals do to a virus?
Inhibit one or more of the steps of viral multiplication
CPE and herpes?
Some herpes can synthesize protein in their envelope to help fuse to host clel
What to spikes find?
Specific receptor site on host cell..
What is the general virus multiplication cycle?
Attachment to host cell
Penetration into host
The uncoating of the virus
Synthesis of viral proteins and DNA using host machinery (usually)
Assembly of the replicated virus from proteins
Release out of the cell
Repeat
Difference in coated pit vs not coated..
Dff but ultimate affect is release of virion into host cell.
RNA virus vs DNA virus synthesis
RNA virus does not need to get into nucleus.. Can translate in cytoplasm (where translation occurs in normal cells…already have RNA!)
DNA virus must get into nucleus to replicate.. Must transcribe RNA prior to translation
Exceptions of where RNA virus and DNA virus replicate
AIDS - RNA virus - replicates in nucleus)
Influenza - RNA virus - (needs enzyme in nucleus of cell to replicate)
Pox viruses - DNA - cytoplasm
Viroporins
Small, hydrophobic virus encoded proteins
Oligomerize at host cell membranes
What are Viroporins involved in?
They are involved in enveloped virus budding
and Enveloped virus cellular lysis
What cytopathogenic effects to viroporins have on cell?
They form hydrophilic pores and alterations of calcium and hydrogen gradients
Draw maturation and budding of an enveloped virus.
viral multiplication ppt slide
Where do naked viruses replicate?
In the cytoplasm of host cell
Then the cell lyses and releases the new virion
Enveloped virion budding
Need host protein and viral protein spike. Then buds out.. Doesn’t necessarily kill cell but .. It modefies the cellular membrane and that results in the body not recognizing it as a normal human cell and the body kills it…**
Virus life cycle
Attach Penetrate Uncoating Transcription of mRNA in cyto or nucleus Translation of proteins Replication of DNA Assembly proteins Assembly of virus (maturation) Release
How to determine how long it takes for a virus to replicate in a host cell?
Find a one step growth curve
What is a one step growth curve?
Viral multiplication ppt
Naked virus
Lyses cell, then to other cells
Eclipase period
First start to see viruses made
Latent period
First see release of virus
Then get burst size
how many are pumped out.
What happens to latent period in cells that are actively replicating vs cells that are not?
Latent period is much shorter in cells that are replicating. The host cell has all of the machinery up and running so to say*
Example of Orthomyxocviruses
Influenza
Example of Retroviruses
HIV
Where to RNA viruses replicate?
Replicate in cytoplasm except for orthomyxoviruses and retroviruses (transcription for these viral mRNAs happen in nucleus)
What senses (+ or -) to RNA viruses have in regards to mRNA?
What is unique about negative sense viruses?
Positive sense (same as mRNA polarity) Negative sense (opposite of mRNA) Ambisence (both positive and negative)
All negative sense RNA viruses are enveloped
What do host cells lac (in cytoplasm) that RNA viruses must produce?
Host cells do not have cytoplasmic RNA polymerase
SO.. RNA viruses must produce their own replicase/transcriptase
What is unique mechanism to produce individual polypeptices from polycistronic RNA?
Picornaviruses synthesize polypeptides that are then cleaved by viral proteases…
Individual initiaion adn termination signals appear throughout RNA of rabies virus
Drugs target viral proteases…Why?
…
Virus with segmented genome*
Each segment codes for one (or sometimes 2) polypeptides required for replication.
Orthomyxoviruses and retroviruses have segmented genomes. (retroviruses have spliced transcripts)
Why is spontaneous mutation frequency higher in RNA viruses vs DNA viruses?
Because RNA polymerases are not as accurate in duplication
What to all negative sense RNA viruses have?
Have a repicase/transcriptase associated with RNA within the virion
What is different about RNA viruses HIV and Influenza?
NEED NUCLEUS FOR REPLICATION**
What do all single stranded RNA replicate via?
except retroviruses, they replcate via?
Double stranded RNA intermediate
Retroviruses have a nuclear phase, involving reverse transcriptase
Where does replication of DNA viruses occur? Why?
In the nucleus.
Because they need the machinery of the host cell.
Exception is poxviruses (happens in cytoplasm)
Where do poxviruses replicate?
They replicate entirely in cytoplasm
What phase of the host cell is needed for DNA virus replication?
S phase*
The availability of host cell DNA binding proteins for transcription helps determin tissue trophism and host range of virus
Non productive infection
need S phase of host function* herpes on lip example.. Must have s phase of cell so factors activeate and allow virus to go town to lip and replicate…
If not in S phase the virus cannot replicate..
All DNA viruses except which can transformm cells?
Parvoviruses
Hepadnaviruses
Partially Double stranded DNA genome (Hep B)
How are hepadnaviruses replicated?
Replicated in nucleus by RNA intermediate, RNA dependent DNA polymerase - reverse transcriptase.. (associated with HIV) sooooo.. Some Hep B treatments are results of HIV treatment research.
Hep B replication happens in hepatocytes*
Pre-genome RNA
Full lenghth copy of DNA, then goes to cytoplasm . It is then reverse transcriptase enzyme makes the DNA.. So have core particle with viral dna that escapes.
Reverse transcriptase
Make DNA from RNA copie using enzyme reverse transcriptase
What DNA viruses have a double stranded DNA genome?
Adenoviruses
Herpesviruses
Papoviruses
What do hepadna (DNA) and retroviruses (RNA) have in commone?
They require reverse transcriptase.. for replication
What DNA viruses have a single strand DNA genome?
Parvovirues
How is singel strand DNA replicated?
How is double strand DNA replicated?
Enters nucleus though nuclear pores
Forms hairpin structure (self primes DNA pol to synthesize complimentary strand
Double stranded DNA uses cellular DNA pol and viral specific endonucleases for form genome
Some strains need a helper virus to replicate (Adeno-associated virus)
Double stranded DNA in Pox viruses
Provide own mRNA and DNA synthetic machinery
Code for viral DNA dependent RNA pols and mRNA modifying enzymes for capping and methylation
They synthesize own envelope
Double stranded dna replication?
Provide own mRNA and DNA.. Do doe they need to be in nucleus?
