Viruses; Structure Classification Replication (Franco Falcone)

Question 1

What are viruses?

Answer 1

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.)

Question 2

Are viruses alive? Grey area

Answer 2

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

Question 3

Where are viruses found?

Answer 3

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.

Question 4

Are viruses always ‘bad’?

Answer 4

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)

Question 5

What are the properties of viruses?

Answer 5

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.

Question 6

How can viruses be classified?

Answer 6

Based on their structure or morphology

• absence or presence of an envelope
• shape of the capsid

Question 7

What is a capsid?

Answer 7

A protein containing viral DNA or RNA which is either helical or isohedral

Question 8

Where does the envelope in some viruses come from?

Answer 8

Lipid bilayer / cell membrane of the host cell that is stolen and used by the virus.

Question 9

Why do viruses chose the icosahedral shape?

Answer 9

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.

Question 10

Why do viruses want to be spherical in an ideal world?

Answer 10

Spheres have the highest volume/surface ratio so can pack a lot without needing to use too much packaging

Question 11

What are the five Platonic solids?

Answer 11

Tetrahedron, hexahedron, octahedron, dodecahedron, icosahedron.

Question 12

What are the features of a viral capsid structure?

Answer 12

They self assemble without the need for additional proteins, following two simple rules.

1. 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).
2. The proteins are linked together by non-covalent bonds. This allows rapid assembly and disassembly of the capsid to release nucleic acid.

Question 13

What is the function of the capsid?

Answer 13

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).

Question 14

What is the difference between a naked and enveloped virus?

Answer 14

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

Question 15

What is the nucleocapsid?

Answer 15

Capsid containing nucleic acid

Question 16

What is a capsomer?

Answer 16

The individual protein molecules which together form the capsid.

Question 17

What is the envelope?

Answer 17

The lipid bilayer derived from the host cells around capsid

Question 18

What is the tegument?

Answer 18

An additional protein layer located between capsid and envelope in some viruses - the same as a matrix

Question 19

What is a virion?

Answer 19

A complete, infective viral particle outside the cell

Question 20

What is the life cycle of a virus?

Answer 20

Attachment 
Penetration 
Uncoating 
Transcription (or reverse transcriptase)
Biosynthesis 
Release and maturation

Question 21

What happens during viral attachment?

Answer 21

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.

Question 22

What does HIV-1 virus bind to?

Answer 22

CD4 and CXCR4 (co-receptor) on T cells

Question 23

What does rhinovirus virus bind to?

Answer 23

ICAM-1 on nasal epithelium

Question 24

What does the influenza virus bind to?

Answer 24

Sialic acid on respiratory epithelium

Question 25

What is ‘Host Range’?

Answer 25

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

Question 26

Give two examples of zoonotic infections

Answer 26

Swine and bird flu

Question 27

What is the preferred route of entry for Rhinovirus and Influenza?

Answer 27

Respiratory tract

Question 28

What is the preferred route of entry for Rotavirus?

Answer 28

GI Tract

Question 29

What is the preferred route of entry of HIV?

Answer 29

Genital tract

Question 30

What kind of routes of entry are possible for viruses?

Answer 30

Skin trauma, transplants, blood transfusions or blood products e.g. hemophiliacs, over 1200 infected with HIV in 1980s.

Question 31

What are viral attachment sites? Where are they found?

Answer 31

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.

Question 32

How do viruses penetrate a host cell and uncoat while they’re inside?

Answer 32

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.

Question 33

How do viruses biosynthesise / replicate?

Answer 33

Viruses need to hijack the cellular machinery to reproduce themselves in a process which involves

1. Making copies of the nucleic acid
2. Producing viral proteins and enzymes
3. Assembling and releasing new viral particles

Question 34

What is the eclipse phase in viral replication?

Answer 34

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.

Question 35

How are the viral proteins and nucleic acids that have been replicated, then assembled?

Answer 35

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.

Question 36

What is maturation of a virus’ life cycle?

Answer 36

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)

Question 37

What is budding?

Answer 37

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

Question 38

How do viruses spread from cell to cell?

Answer 38

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

Question 39

How do viruses cause cellular damage?

Answer 39

They can cause direct damage via cytopathic effects/

Question 40

What are cytopathic effects?

Answer 40

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