Viruses; Structure Classification Replication (Franco Falcone) Flashcards
What are viruses?
Small, sub-cellular organisms with an obligate parasite intracellular lifestyle. They are composed of proteins and nucleic acids (and in some cases, lipids, when stolen from the membrane of a host.)
Are viruses alive? Grey area
They cannot reproduce on their own but can do so in living cells and can also affect the behaviour of their hosts profoundly. They play a major role in shaping evolution, including their own
Where are viruses found?
Viruses are ubiquitous (every living organism can host viruses including bacteria, fungi, animals and plants)
Each of us is infected with at least two viruses
Many viral infections are persistent (once infected, always infected).
Can become part of the host genome and be transmitted to future generations.
Are viruses always ‘bad’?
Viruses play a key role in the life cycle of aquatic environments
They can be used to treat bacterial infection (bacteiophage therapy)
80% of the human genome is of viral origin (retroviruses)
What are the properties of viruses?
Viral genomes (DNA or RNA) are packaged into particles necessary for transmission between hosts
The viral genome contains the information needed for replication within a permissive host cell.
Viral survival is ensured by establishing its genome in a host cell population
All viruses are obligate intracellular parasites - they need the cellular machinery (ribosomes tRNA etc) to replicate themselves.
How can viruses be classified?
Based on their structure or morphology
- absence or presence of an envelope
- shape of the capsid
What is a capsid?
A protein containing viral DNA or RNA which is either helical or isohedral
Where does the envelope in some viruses come from?
Lipid bilayer / cell membrane of the host cell that is stolen and used by the virus.
Why do viruses chose the icosahedral shape?
Icosahedron - 20 identical sides - nearest geometrical shape to a sphere
The structure can be built from multiple repetitions of a single gene / protein –> genetic economy.
Why do viruses want to be spherical in an ideal world?
Spheres have the highest volume/surface ratio so can pack a lot without needing to use too much packaging
What are the five Platonic solids?
Tetrahedron, hexahedron, octahedron, dodecahedron, icosahedron.
What are the features of a viral capsid structure?
They self assemble without the need for additional proteins, following two simple rules.
- Each capsid subunit has identical bonding contacts with its neighbouring proteins. This is usually achieved by symmetrical assemblies of oligomers (mainly pentamers or hexamers of a single protein).
- The proteins are linked together by non-covalent bonds. This allows rapid assembly and disassembly of the capsid to release nucleic acid.
What is the function of the capsid?
The capsid provides protection for the nucleic acid outside the cell (but needs to be released once inside the host cell).
Capsid is made from multiple subunits, which are not covalently linked. Symmetry provides maximal contact points between subunits.
Capsid is metastable i.e. spring-loaded during assembly so that it can unfold in the cell as conditions change i.e. pH
Provides a specific attachment to cell receptors (for naked viruses).
What is the difference between a naked and enveloped virus?
Enveloped viruses are sensitive to: dryness, heat, detergents, acids. This means they must stay wet to be transmitted and do not survive in the GI tract. e.g HIV-1
Naked viruses are resistant to dryness, heat detergents, acids and proteases. This means that they can remain infective in these conditions and can be transmitted via fomites, survive in the GI tract and survive in environment on surfaces. e.g. Adenovirus
What is the nucleocapsid?
Capsid containing nucleic acid
What is a capsomer?
The individual protein molecules which together form the capsid.
What is the envelope?
The lipid bilayer derived from the host cells around capsid
What is the tegument?
An additional protein layer located between capsid and envelope in some viruses - the same as a matrix
What is a virion?
A complete, infective viral particle outside the cell
What is the life cycle of a virus?
Attachment Penetration Uncoating Transcription (or reverse transcriptase) Biosynthesis Release and maturation
What happens during viral attachment?
Viruses bind to specific receptors on host cells etc
This specific attachment confers the viruses a preference for specific cell types/tissues, called a cell tropism and a specific host range.
What does HIV-1 virus bind to?
CD4 and CXCR4 (co-receptor) on T cells
What does rhinovirus virus bind to?
ICAM-1 on nasal epithelium
What does the influenza virus bind to?
Sialic acid on respiratory epithelium
What is ‘Host Range’?
Host range is defined as the ability of a virus to infect different species e.g.
- Rabies has a wide host range, it can infect all mammals to a various degree
- HIV has a narrow host range, it can only infect humans
Give two examples of zoonotic infections
Swine and bird flu
What is the preferred route of entry for Rhinovirus and Influenza?
Respiratory tract
What is the preferred route of entry for Rotavirus?
GI Tract
What is the preferred route of entry of HIV?
Genital tract
What kind of routes of entry are possible for viruses?
Skin trauma, transplants, blood transfusions or blood products e.g. hemophiliacs, over 1200 infected with HIV in 1980s.
What are viral attachment sites? Where are they found?
Attachment sites on host cells frequently found in lipid rafts
Lipid rafts are special regions of the cell membrane that are rich in cholesterol and sphingolipids, providing densely packed, more rigid regions that are more suitable for stable attachments to the cell surface.
How do viruses penetrate a host cell and uncoat while they’re inside?
Enveloped viruses fuse with the host cells plasma membrane followed by capsid disassembly (uncoating).
Non-enveloped viruses do not have the lipid bilayer to fuse so the whole virus must be taken up. It is inserted into a coated pit. Clathrin forms underneath. A vesicle forms an endosome and takes up the virus.
How do viruses biosynthesise / replicate?
Viruses need to hijack the cellular machinery to reproduce themselves in a process which involves
- Making copies of the nucleic acid
- Producing viral proteins and enzymes
- Assembling and releasing new viral particles
What is the eclipse phase in viral replication?
For viruses to reproduce inside the host cell they need to replicate their nucleic acid, which will then be packaged into new capsids and released.
The virus only has a small number of genes so relies on the host cell machinery for its replication.
This phase begins immediately after the virus has entered the host cell. This is known as the eclipse phase because no signs of the virus can be seen yet.
How are the viral proteins and nucleic acids that have been replicated, then assembled?
After production of viral proteins and nucleic acids, these need to be assembled into new virions
Assembly occurs a specific points in the cell depending on the virus
Packaging of nucleic acids into capsid occurs through a spontaneous self-assembly process.
What is maturation of a virus’ life cycle?
After self assembly, the virus may still be non-infectious.
Maturation may involve proteolytic cleavage by viral or cellular proteases
- HIV gag polyprotein by HIV protease (a viral protease)
- Influenza A haemagglutinin by transmembrane protease serine 2 (a cellular protease)
What is budding?
Following assembly, budding may be needed to release newly assembled viruses by the infected cells.
Not all viruses are released by budding.
HIV, influenza and measles are released by budding.
If viruses are not released by budding they are often ‘lytic viruses’ ; once mature the cell they had infected, bursts open and dies. Poliovirus is a lytic virus
How do viruses spread from cell to cell?
Apical - movement of virions through the apical side of the cell i.e. the lumen.
Baso-lateral is from cell to cell e.g. Herpes
Moves between tight junctions of neighbouring cells
How do viruses cause cellular damage?
They can cause direct damage via cytopathic effects/
What are cytopathic effects?
Cell lysis; cells burst open to release new virions
Cell fusion; several cells are fused together as viruses move between them resulting in multi-nucleated syncitia
Transformation; DNA or RNA tumour viruses may mediate multiple changes that convert a normal cell into a malignant one (oncogenic viruses).
DNA damage; following viral infection, breakage, fragmentation, rearrangement and or changes in the number of chromosomes may occur
