Virology Flashcards
Virus Definition
a small non cellular agent consisting largely of nucleic acid within a protein coat requiring a host cell for replication
- not considered alive
Virus vs. Life Form
Virus:
- no metabolism
- multiple origins
- assembly
Viral Genome Diversity
- DNA or RNA
- double or single stranded
- circular or linear
- +/- sense
- segmented or nonsegmented
Virion particle
an entire virus particle, consisting of an outer protein shell called a capsid and an inner core of nucleic acid
- is infectious
DNA vs RNA Genomes
- DNA viruses often larger in genome size because of the proofreading enzyme ability
- RNA is less stable
- overlapping genes common
eg. HIV-1 has 4 genes in different reading frames
Double or single stranded
- most RNA viruses are ss (except reoviruses)
- regions of dsRNA and intracomplementarity within the strand
- most DNA viruses are ds as this is more stable
Circular or linear
- most are linear
- circular viruses often in phages
- DNA viruses can be circularized for a period in the life cycle
- circular viruses will be persistent in the cell (replicated)
Negative sense viruses
3’-5’
- copy to make + sense mRNA for translation
- make into 5’-3’ direction for host cell translation
Positive sense viruses
5’-3’
- can be directly translated by host into progeny
Non-segmented vs Segmented
non-segmented: mono-partite
segmented: multipartite
eg. retroviruses have + sense non-segmented genome
Influenza Virus
- ve sense segmented genome
- genome encoded on little ‘chromosomes’ with 1/2 proteins
- evolves by mutation, recombination (within single piece of genome), or reassortment
- reassortment is the exchange of entire segments for another virus
- antigenic shift: RNA segments exchanged between viral strains in secondary host (no cross protective immunity to novel virus)
Virus structure
- genome surrounded by capsid protein coat
- The core confers infectivity, and the capsid provides specificity to the virus
- sometimes you get a host lipid envelope
Tobacco Mosaic Virus
+ sense RNA
- capsid protecting the RNA core
- 4 capsid proteins replicated in the cell
Capsids
- assembly of monomeric protein units can produce spherical particles
- gives shape and structure
- auto-assembly without host help
- many symmetrical possibilities which affect host cell binding
Ebolavirus
- some viruses have an envelope in addition to a capsid
- capsid differentiated
- lipid membrane derived from host
- envelope proteins on the surface bind to the host membrane receptor proteins
Viral Hosts
- some viruses are host specific (smallpox or polio)
- eradication possible because of a lack of a reservoir
- reservoir hosts: natural infected animal/may not be symptomatic
- vector: animal transmitting disease
- dead end host: virus in host not sufficient for transfer back to mosquito
eg West Nile Virus in birds
Mimivirus
- related to other viruses
- may represent a new ‘life form’
- large genome size (900 genes) and physical size
- produce virion factories
- ‘alive’ in the way a seed is
Steps in Viral Replication
- infection and disassembly of infectious particle
- uncoating of nucleic acid core - replication of viral genome
- synthesis of viral proteins by host machinery
- transcription/translation - reassembly into progeny virus particles + maturation
- burst exit from cell
- genome specific
Replication Phases
- eclipse phase: enter host and start takeover (low viral load)
- maturation and release phase
- decay phase: virus doesn’t survive as virion particles
Host Cell Attachment
- recognise cellular receptors of cell surface
- determines which cells can be infected
HIV-1 Receptors
- retrovirus
- recognises 2 receptors
- can switch receptors during infection (macrophages vs T cells)
- this is called cellular tropism
Host Cell Infection/Disassembly
- fusion or endocytosis
- uncoating (disassembly)
HIV Infection
Enveloped:
- fusion and uncoating of virus injects RNA into cell
- leaves envelope on surface
- binding triggers conformational change for fusion
Influenza Infection
RNA:
- binds to cell surface
- induces cell endocytosis and virus inside endosome
- cell pumps in H+ (acidification) and this causes conformational change, fusion, and uncoating
- nucleic acid in cytoplasm
Poliovirus Infection
RNA:
- no envelope = no fusion
- binds to receptor
- binding causes complex series of event ending in viral RNA moved through pore in vesicle
Adenovirus Infection
DNA:
- endocytosis and lysis of vesicle
- nuclear localisation signal on capsid surface locating to nuclear pore
Genome Replication
- DNA viruses replicate in the nucleus (except poxvirus)
- RNA viruses replicate in cytoplasm (except retroviruses)
- produces polypeptide that is cleaved by proteases
ssRNA (+) replication
- negative strand RNA synthesis: positive strand RNA synthesis : forms virion particle
- host cell translation of initial positive sense RNA into capsid proteins and RNA pol/dep that synthesize -/+ sense RNA for formation of virus
ssRNA (-) replication
- need an RNA dependent RNA polymerase
- virion particle contains virion polymerase attached to RNA
- RNA dep/pol synthesizes positive RNA from negative strand
- positive sense RNA is translated into more viral polymerase/capsids
- also made back into negative RNA by virion polymerase for formation of new virus particles
dsDNA replication
- need insertion into nucleus
- DNA replication (host or viral) for new virus particles
- DNA transcription (inside nucleus) and translation (outside nucleus) into capsids/DNA pol
- assembly in nucleus at site of DNA replication
retrovirus replication
- carry reverse transcriptase to make DNA out of RNA
- integrate into the genome
- in nucleus, reverse transcriptase goes from RNA to dsDNA
- integration
- transcription and translation from genome
- synthesis of reverse transcriptase, RNA, and capsid
- formation of virus particle
Host proteins and virus replication
- transcription often uses host polymerases
- host TF bind to viral RNA to control expression
- translation uses host ribosomes
- polypeptides cleaved with host proteases
Virus Assembly
- capsid assembly generally occurs at site of genome replication (often self assembly with simultaneous binding of viral genome to capsid protein)
- viruses with envelopes are assembled either on cell surface or in sub-cellular compartments
- viral membrane derived from host cell
Retrovirus surface assembly
1) no envelope: lyse cell
2) envelope: lyse or bud
- capsid containing viral chromosome
- nucelocapsid induces assembly of transmembrane envelope proteins
- budding off and formation of progeny virus
Smallpox subsurface assembly
- replicate in viral factories with different morphologies
IMV: efficient at new host infection ; 2 membranes/needs lysis
EEV: infect other cells in same organism (longe range spread) ; 3 membranes/exocytosis
CEV: induces actin tail from cell to deposit CEV onto short range neighbour cell)
Types of Viral Infections
- permissive: cells supporting viral infections
- productive infection leads to cytopathic effects if acute
- infection of non permissive cells leads to abortive infection where host cell stops replication
- a persistent infection is chronic
- viruses can transform cells via abortive infection or oncogenesis (cause mutations and damage or turn on/insert oncogene)
Host Cell Morphological Changes
- nuclear inclusion
- cytoskeleton
- giant cell formation
- syncytia: fusion of viral envelope with uninfected cells to make giant cells
Host Cell Biochemical Changes
- activation of cellular protein kinases/TFs
- activation of oncogenes/cell cycle arrest
- inhibition of DNA synthesis
Host Cell Defences
- induced defenses
- non-induced defenses
Induced Defenses
- interferon stimulation of cells causes ‘viral state’
- infection upregulates production in cells
- warns uninfected cells to turn on defences
- targets points in viral replication cycle by inducing protein production
1. transcription inhibitors
2. translation inhibitors
3. protein processing inhibitor
4. virus maturation inhibitor
Translation Inhibitory Protein
- recognises cap snatching from hist mRNA
- slows ribosome speed to stop viral RNA production
Retrovirus Transformation
- isolated from chicken fivrosarcoma
- is a tranforming virus causing cancer
- generated when cellular protooncogene captured by insertion into viral genome during viral replication
- can then be passed on to further hosts
- oncogene is Src protein tyrosine kinase: virus didn’t capture bit cells use to turn this kinase ‘off’
- oncogene beneficial to virus as it causes cell growth