W21 Virus structure, viral replication cycle and prions Flashcards
Virus general characteristics:
- 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)
What are the misconceptions about viruses?
Viruses are NOT bacteria
* Antibiotics are not effective against viruses
* Specific virus infections should be treated with antiviral agents
How can viruses be seen?
Virus particles can only be seen through electron microscopy (not by a light microscope)
Virus nomenclature/taxonomy: (for info)
- Classification:
- Family names end in –viridae
- Genus and species names end in -virus.
Virus composition:
What is a virion?
What does it comprise of? (3)
= Complete, fully developed viral particle composed of:
-Nucleic acid
-Capsid
-Envelope
Virion composition:
What is a nucleic acid?
-Nucleic acid: DNA or RNA can be single or double-stranded; complexed with matrix proteins or enzymes
Virion composition: What is a capsid?
Protein coat/shell to protect the nucleic acid
Virion composition: What is the envelope?
-Envelope—lipid bilayer membrane (Host cell derived) on some viruses, in which some peripherical glycoproteins (e.g. Spikes) projects from outer surface
Virus particle/virion composition:
- Covering:
-Capsid structure
-Envelope (not always present) - Central core:
-Nucleic acids (DNA/RNA)
-Matrix proteins/ enzymes (depends on virus)
Presence/absence envelope
Naked or enveloped viruses
* External layer of a virion
* Not always present
-Not present in rhinoviruses, adenoviruses, etc. (naked viruses)
-SARS-CoV-2, HIV, herpesviruses, influenza viruses possess it (enveloped)
What is a Viral envelope?
Are enveloped viruses strong?
- External layer of a virion
- 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
Enveloped viruses are more susceptible to
chemical disinfectants
Features of Envelope glycoproteins :
What are they?
Where are they synthesised?
What are they involved in?
- Transmembrane glycoproteins (encoded by the viral genome) that protrudes outside the envelope
-Synthesised through the secretory pathway – destined to the plasma membrane - Involved in binding specific protein receptors on the external surface of the host’s cell (viral absorption, the first step)
- Sometimes involved in viral-cell fusion
- In some viruses, those external proteins have other names e.g. hemagglutinin and neuraminidase in influenza viruses
Viral capsid features:
- 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
What are the shapes of different capsids?
- Helical- hollow, cylindrical
- Polyhedral- Many-sided
- Complex- complicated structures
What are Viral genomes?
- Viruses contain either DNA or RNA
- Can be double-stranded (ds) or single-stranded (ss), linear or circular
- Low size genomes - Hepatitis B (4 genes), herpesviruses (100 genes)
- No viral metabolic genes, as the virus uses the host’s metabolic resources
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)
Spectrum of a viral infection:
How do viruses bind to receptors?
What are bacteriophages?
- The spectrum of host cells a virus can infect is usually narrow
- Most viruses infect only (or a few) specific types of
cells in one host (defined as viral tropism) - Mainly determined by the presence of specific
receptors on the surface - Also, cells should have cellular factors capable
of replicating virus - Different viruses can bind the same receptor
- Viruses of the same family may bind different receptors
Bacteriophages or phages - viruses that infect only bacteria
Viral replication cycle (generic)
- Human viruses undergo a series of events to enable the replication (multiplication) inside a host’s cell
- Steps change from virus to virus
- Some viruses have additional steps
(e.g. HIV – genome integration)
What are the 6 viral replication steps? (brief)
- ATTACHMENT- A generic virus becomes attached to a target epithelial cell
- PENETRATION- The cell engulfs the virus by endocytosis
- UNCOATING
What occurs in Viral attachment?
- 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)
What occurs in STEP 2 – Virus penetration – Membranes fusion? (2 steps)
- After attachment, viruses need to penetrate the cell (2 ways)
- Enveloped viruses: by fusion of viral envolope and host cell membrane
-mediated by viral fusion proteins (on the envelope) - 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)
What occurs in STEP 3 – Virion uncoating - Genome release?
- Virion uncoating: stepwise process of disassembly of the virion to release the genetic material in the nucleus of the cell
What occurs in STEP 4: Virus genome replication and protein synthesis?
- Viruses hijack the host cell synthesis machinery to:
- Replicate their genome
- Produce their proteins (Transcription of viral genes into mRNA and protein translation)
- This step depends on the type of nucleic acid carried by the virus
What occurs in STEP 5 – Assembly of NEW virions?
- 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 - This happens in proximity to the plasma membrane
- 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
What occurs in STEP 6 – Release of new virions?
Release. Completed viral particles exit the cell and can infect other cells.
* Mechanisms of virion release differ 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 are not destroyed
b) Lysis – Naked viruses - Viruses are released only when the cell dies
What are Prions?
- Proteinaceous infectious particles – misfolded proteins
- Prions do not contain nucleic acids
- Cause transmissible spongiform encephalophaties fatal neurodegenerative diseases
-Mad cow disease“ (BSE)
-Creutzfeldt-Jakob disease (CJD)
-Sheep scrapie
Prions
* Inherited and transmissible by ingestion
(common in animals), transplant, and surgical instruments
- Extremely resistant to standard sterilization
techniques:
-Such as standard autoclave programs of 121o C
for 15 minutes (more than bacterial endospores) - Prion inactivation requires autoclave cycle at
134°C for 18 minutes or more
