Introduction to Viruses Flashcards
Describe the basic features of Viruses
Small infectious agent that replicates by infecting the cells of a host organism
Obligate intracellular pathogens
Size: Ranges 20 - 300 nm
Composed of nucleic acid surrounded by a protein coat
Most viruses can only infeft specific cell types
E.g Skin cells, respiritory cells
This is the virus tropism (nature in which they target)
They have various shapes: icosahedral, helical & complex
What are the key components in a mature virus?
Nucleic acid (genome)
Surrounded by a protein coat (capsid)
Some have Virulence factor (embedded proteins)
Help virus enter a cell
Some have lipid envelopes
These can fuse with the lipid envelope on other cells
What is the virus genome?
Circular or linear
Can be any of the following:
SS RNA
DS RNA
SS DNA
SD DNA
If it is single stranded it can be either positive or negative sense
-Positive sense
Sequence can code directly for virus protein
-Negative sense
Reverse complement to positive sense doesn’t typically code for protein
*genome type influences how viruses make mRNA
What are the functions of the viral proteins?
-Structural proteins encode:
Capsid
outer coat of the virus protects the nucleic acid - may also serve to allow the virus to
bind to target cells **
Nucleocapsid
simpler structure – proteins closely associate with virus genome
Envelope glycoproteins
embedded in lipid membrane of enveloped viruses mediate recognition of host
cells and entry **
** NB Major recognition sites of antibodies
-Non-structural (NS) proteins
Mediate replication of genome
i.e. polymerases
May have role in suppressing the immune system (e.g. NS1 in influenza) or changing
the cellular environment
-Accessory Proteins
Special functions, usually in restricted cell types
e.g. orfA in feline immunodeficiency virus promotes replication in lymphocytes
What is the lipid envelope?
Derive envelopes from cell membranes by budding
Plasma membrane
E.g. Influenza, retroviruses
Nuclear membrane
E.g. Herpesviruses
Internal organelles
E.g. coronavirus
What is the clinical relevance of the lipid envelope?
Enveloped viruses tend to be more unstable to heat, pH extremes, detergent
Describe the basic features of Prions (TSE)
Prion disease:
Proteinaceous infectious particle (Prion protein: PrP) Unusual (contentious!) disease PrPc is a cellular protein ~250 amino acids. Expressed mostly in the CNS
Normally exists in one shape (pN) – but can “misfold” (pD) leading to the formation of large protein aggregates. pD seems to propagate more misfolded protein which leads to brain dysfunction and fatal disease
How are TSE’s spread?
TSEs are spread by puncture contact, or ingestion.
They can spread by infecting nerve cell ends and lymph cells.
Spleen seems to be a major site of infection prior to CNS
They can also be spread by invasive techniques such as surgery
Describe how viruses are classified
Classified based on Genome
Baltimore Classification Scheme
DNA or RNA Single Stranded or Double Stranded Negative or Postive sense
What does phylogenetics mean in relation to viruses?
Determine how related viruses are to one another
‘study of evolutionary relationships between biological entities’
Uses genetic comparisons between related viruses
Outline how Feline Calicivirus is grouped based on its genome sequence?
Determined by:
International committee on taxonomy of viruses (ICTV)
(Order):
Not assigned
Family:
Caliciviridae
(sub family):
Genus:
Vesivirus
Species:
Feline calicivirus
How do viruses infect the host?
- Must infect cells which support viral replication
- Require appropriate receptors for cell entry
Sialic acids for influenza
Transferrin for feline parvovirus - Must ensure cell physiology is appropriate
Supplies replicative enzymes, ATP, nucleotides, other proteins
What are the replication strategies of viral replication?
Virus needs to exploit normal cell processes
Either infect specific cells/cell compartments which provide “what they need” Or encode proteins that they require or which alter the cell metabolism
Why do some viruses use polymerase enzymes provided by the host?
Replicate viral genetic material to produce mRNA (protein) and genomic nucleic acid
-provided by cells Or -provided by virus
If suitable polymerase is not provided by cell or not found within the compartment which the virus replicates then the virus must supply polymerase. This is the case with many RNA viruses
How does viral ssDNA replicate?
Parvoviruses, circoviruses
Require active host DNA polymerase to replicate genome
i.e. Produce dsDNA
These viruses can only infect dividing cells where DNA polymerase is active
Use host RNA polymerase to produce mRNA
Parvovirus: infect intestinal cells, bone marrow cells, cardiac & neural cells
How does viral positive sense ssRNA replicate?
Picornavirus e.g foot & mouth disease
Virus RNA can act directly as mRNA
Genome is directly infectious
RNA translated to produce single polyprotein
This protein is then cleaved by viral proteases
Genome replicated by viral polymerase (through negative sense strand template
How does viral negative sense ssRNA replicate?
Virus RNA cannot act directly as mRNA
Virions contain (and genome encodes for)
RNA dependent RNA polymerase
Generates +ve sense mRNA
Genome also replicated by viral RNA polymerase, via +ve sense intermediate
Typically replicate in cytoplasm e.g paramyxoviruses
EXCEPT bunyaviridae and orthomyxoviridae
How is retrovirus transcribed?
The viral RNA is reverse transcribed:
viral reverse transcriptase [RNA-dependent DNA-polymerase] converts genome to complimentary DNA (cDNA)
This cDNA integrates into the chromosome of the host cell by viral integrase enzyme:
This integrated DNA is termed proviral DNA
The integrated DNA then produces RNA and protein using normal cell machinery
Integration into host genome is permanent (for life of cell)
Can disrupt normal genome activity and lead to tumour formation
Describe how viruses can cause disease
Transformation of normal cells to tumour cells
e.g. feline leukaemia virus & Bovine papilloma virus
Lytic Infection (death of cell & release of infection)
e.g. foot and mouth disease
Persistent infection (slow release of virus without death)
e.g. retroviruses
Latent Infection (virus present but not causing harm to the cell; later emerges into lytic infection
e.g. Herpes virus
What are the implications on the animal during a viral infection?
Clinical
Cell death & tissue damage
Host response to infection
Cancer
Sub Clinical
Can cause problems when controlling disease in a population
Transmission to susceptible animals Undetected effects (fertility problems, poor 'form') Latent viruses – “hide away” with potential for later disease
What are the factors which affect the clinical outcome (virus, host & environment)
Virus:
Virus strain (pathogenicity)
Virus load
Host:
Genetic – immune system genes (e.g. MHC)
Receptors
Age (immune system, receptor expression, dividing tissues, passive immunity)
Pre-existing immunity
Physiological status
Concurrent infection
Environment:
Overcrowding, Ventilation
Outline the ways viruses create genetic variation?
Spontaneous mutation
Gene transfer between viruses
Recombination
Gene Reassortment
What are spontaneous mutations?
Mistakes made during genome replication
RNA viruses higher rate of mutation (enzymes cannot proofread)
10 000 bp RNA virus - average 1 mutation per new genome
cf. DNA viruses mutation rate – 1 in 108 nucleotides
Very high replication rate of some RNA viruses means very large numbers of mutant viruses (e.g. HIV 109 viruses/day)
What is meant by gene transfer between viruses?
Transfer of genetic information between two, usually related, viruses which have infected the same cell
Production of hybrid genomes
– entire gene(s)/gene segments derived from another virus
Mechanisms
Recombination
Reassortment (segmented viruses)
Viruses (/or cell)
What is recombination?
Relatively rare: occurs between viruses with related DNA/RNA sequence or
Between virus and host nucleic acid
Can lead to viruses acquiring host sequences
What is meant y gene reassortment?
Can occur for viruses with a segmented genome
Simple exchange of genes can occur when two different viruses infect a cell
e.g. influenza, rotaviruses
Rapid evolution of virus variants
Can combine with other viruses and change apart of its gnome making it more resistant to immune system
What are the consequences of viral mutations?
Lethal mutation, silent mutation, growth advantage/disadvantage
Circumstances which limit the ability of the virus to persist (e.g. immune response) , favour emergence of mutants which are better equipped for survival
