Virus structure, viral replication cycle & prions Flashcards
Viruses
The most abundant biological entities on Earth
An estimated 10 nonillion (1031) individual viruses
The length of a head to tail line of 1031 viruses is around 100 million light years
- infect living things
What are the general characteristics of viruses?
NOT CELLS – Acellular Infectious particles
After prions, viruses are the smallest infectious agents (10 to 400 nm in diameter)
Different sizes and shapes
Do not grow or undergo division outside a cell
Obligate intracellular parasites - Requires a host for replication
they need the machinery and metabolism of a host cell
Are produced by replication from the assembly of pre-formed viral components
Carry genetic material either DNA or RNA (not both)
Viruses are NOT bacteria
- Antibiotics are not effective against viruses
- Specific virus infections should be treated with antiviral agents
What type of microscope can you see viruses through?
electron microscope
Classification:
virus
Family names end in –viridae
Genus and species names end in -virus.
Viral species: Common names are used for species.
Subspecies are designated by a number.
Virus composition
Nucleic acid - DNA or RNA can be single- or double-stranded; complexed with matrix proteins or enzymes
Capsid—protein coat/shell to protect the nucleic acid
Envelope—lipid bilayer membrane (Host cell derived) on some viruses, in which some peripherical glycoproteins (e.g. Spikes) projects from outer surface
Virion
complete, fully developed viral particle
flow diagram of viral composition
Ririon or virus particle > covering / central core > capsid structure ./ envelope / nucleic acids (DNA or RNA) / matrix protein / enzymes (depends on virus)
Presence/absence envelope
Naked or enveloped viruses
= external of a virion
envelope not always present
Not present in rhinoviruses, adenoviruses, etc. (naked viruses)
SARS-CoV-2, HIV, herpesviruses, influenza viruses possess it (enveloped)
Where is the Viral envelope located?
external layer of a virion
What is the viral envelope made out of?
Envelope is a lipid bilayer derived from host cell (infection’s final step)
Viral genome does not encode lipid synthetic machinery
Envelope acquired by budding of capsid when viruses leaves the cell
Viral envelope glycoproteins
Transmembrane glycoproteins (encoded by the viral genome) that protrudes outside the envelope
Synthesised through the secretory pathway – destined to the plasma membrane
What is the role of envelope in virus made out of glycoproteins?
Involved in binding specific protein receptors on the external surface of the host’s cell (viral absorption, the first step)
involved in viral-cell fusion
What is a Viral capsid?
Large and protective shell that surrounds/protects viral nucleic acid –
Also called nucleocapsid
Composed of many capsomers (identical subunits - like the pieces of a puzzle)
Each one has ‘identical’ and reversible bonding contacts with its neighbours
Capsid shape
3 types
- helical - hollow, cylindrical
- Polyhedral - many-sided
- Complex - complicated structures
Viral genomes - Nucleic acid
contain either DNA or RNA
double-stranded (ds) / single-stranded (ss),
linear / circular
Viral genomes possess only the genes to encode proteins involved in:
The structure of the virion (capside protein, envelope glycoproteins)
Invading the host cells and hijacking/regulating its metabolic activity to produce more viral proteins and quench the production of cellular
proteins
Enzymes to reproduce/multiply their genomes (e.g. DNA/RNA polymerases)
Virus can only infect a small amount of _____ cells
host
Viral tropism
Most viruses infect only specific types of cells in one host
How is viral tropism determined?
- presence of specific receptors on the surface
- cellular factors capable of replicating virus
Can different viruses bind on the same receptor?
yes
Viruses of the same family may bind ________ receptors
different
Viral replication cycle (generic)
a) Human viruses undergo a series of events to enable the replication (multiplication) inside a host’s cell
b) Steps change from virus to virus
c) Some viruses have additional steps (e.g. HIV – genome integration)
STEP 1 – Viral attachment
[viral replication]
Virus adheres to cell surface (random collisions & electrostatics)
No specificity required
Attachment to specific receptors on cell surface by envelope glycoprotein or protruding capsid protein (naked viruses)
STEP 2 – Virus penetration – Membranes fusion
[viral replication]
After attachment, viruses need to penetrate the cell
2a. Enveloped viruses: by fusion of viral envelope and host cell membrane mediated by viral fusion proteins
2b. Naked viruses (e.g. Adenovirus, Adv): enter cells by endocytosis
Receptor binding triggers the process of endocytosis
Cell membrane is pinched off
The virus is engulfed
A vesicle is formed (Endocytosis)
STEP 3 – Virion uncoating - Genome release
[viral replication]
disassembly of the virion = release the genetic material in the nucleus of the cell
STEP 4 – Virus genome replication and protein synthesis
[viral replication]
Viruses hijack the host cell synthesis machinery to:
Replicate their genome
Produce their proteins (Transcription of viral genes into mRNA and protein translation)
STEP 4 – Virus genome replication and protein synthesis
[viral replication]
Viruses hijack the host cell synthesis machinery to:
Replicate their genome
Produce their proteins (Transcription of viral genes into mRNA and protein translation)
STEP 5 – Assembly of NEW virions
[viral replication]
a) New genome copies and many capsid subunits are synthesised
Through the endomembranous system, envelope glycoproteins are synthesised by the cell and sent to the plasma membrane
b) Capsid subunits assembled together to form a capsid
The replicated viral genome and some viral proteins become packaged within
From a single infected cell – 104 / 106 new virions are produced
STEP 6 – Release of new virions
[viral replication]
Release. Completed viral particles exit the cell and can infect other cells.
mechanisms vary between NAKED and ENVELOPED viruses
a) Budding / exocytosis – enveloped viruses - new capsid particles bind the membrane, the membrane pinches off and viruses acquire the envelope and there are released = cells NOT destroyed
b) Lysis – Naked viruses - Viruses are released only when the cell dies
Prions
Proteinaceous infectious particles – misfolded proteins
Do prions contain nucleic acid?
no
What does prions cause?
Cause transmissible spongiform encephalophaties fatal neurodegenerative diseases
“Mad cow disease“ (BSE)
Creutzfeldt-Jakob disease (CJD)
Sheep scrapie
*Inherited and transmissible by ingestion (common in animals), transplant, and surgical instruments
What is Spongiform encephalopathies?
Rapid and progressive neurodegenerative disorders
- Long incubation periods
- Impairment of brain function
- Mental and physical abilities rapidly deteriorate
- Always fatal
Spongiform encephalopathies - appearance
Many tiny holes appear in the cortex causing it to appear like a sponge
Explain why prions are extremely resistant to standard sterilization?
Extremely resistant to standard sterilization techniques:
such as standard autoclave programs of 121°C for 15 minutes (more than bacterial endospores)
Prion inactivation requires autoclave cycle at 134°C for 18 minutes or more
List the types of viruses from most to least resistant to standard sterilisation:
1) Prions
2) Endospores of bacteria
3) Mycobacteria
4) Cysts of protozoa
5) Vegetative protozoa
6) Gram -ive bacteria
7) Fungi, incl. most fungal spores
8) Viruses w/o envelopes
9) Gram+ive bacteria
10) Viruses with lipid envelopes
