lecture 9 - viruses 1

Question 1

What are the basic features of viruses?

Answer 1

Nucleic acid surrounded by protective protein coat
• Replication is host cell-dependent (obligate parasites) - they cannot divide without using the machinery of the host cell
• Have intracellular and extracellular phases
Spread not by cell to cell contact but by lysing of the cell

Question 2

What are the basic functions of viruses?

Answer 2

they are introduced into a population
they spread (infect/replicate/infect)
Note: Not only humans are infected by viruses.
Viruses infect animals, plants, protozoans, even bacteria!
they escape our body’s defenses
they cause disease
they are a major cause of death (mortality) or
reduced quality of life (morbidity) worldwide

Question 3

What are the different strategies viruses use to escape the body’s defences?

Answer 3

The “city” virus
These change very quickly to escape becoming recognizable to the immune system
playing a fitness cost game.
The “buy what I can afford” virus
These are old enough to have developed safe ways to evade detection by our
immune system.
The “infect whatever moves” virus
These are not particularly good at escaping our defenses, but so highly infectious
that they spread to the next person before our responses can destroy them.

Question 4

What are some different kinds of viruses?

Answer 4

Orthomyxovirus:
influenzas
Picornoviruses:
polio, rhinovirus (colds), Hepatitis A
Herpesvirus:
herpes simplex, chicken pox, EBV (mono)

Question 5

What is the extracellular phase of a virus called?

Answer 5

Virion

Question 6

Describe virion structure

Answer 6

Virion structures vary widely in
shape and chemical composition

• Nucleic acid surrounded by
protective protein capsid
• Capsid form is highly repetitive
Enveloped virus uses part of host cell membrane to bud off and attach to other host cells.

Question 7

How does infection of target cells take place?

Answer 7

Attachment to host cells is mediated by protein spikes on the surface of viruses, which bind to host surface molecules (often glycoproteins) known as viral receptors
1- Membrane fusion:
adsorption - spikes of virion attach to specific host cell receptors
envelope of virion fuses with plasma membrane
nucleocapsid released into cytoplasm - viral envelope remains part of plasma membrane
nucleic acid separates from capsid coat protein
2-Endocytosis:
Adsorption of virion to host cell - endocytosis begins
plasma membrane surrounds the virion - vesicle forms
envelope of virion fuses with plasma membrane of host - nucleocapsid released from vesicle
Nucleocapsid is free within host’s cytoplasm
Separation of nucleic acid from capsid protein

Question 8

How does budding to form a new virion take place?

Answer 8

Viral proteins that are to become spikes of virus attach to host plasma membrane
Viral matrix protein coats inside of plasma membrane
Nucleocapsid becomes enclosed by viral envelope ‘s which is composed of the host’s plasma membrane

Question 9

What are the consequences of viral infection?

Answer 9

Transformation of normal cells to tumour cells
Replication inside the cell causes cell lysis and death of cell and release of virus - lytic infection
Slow release of virus without causing cell death - persistent infection
Virus present but not causing harm to cell; later emerges in lytic infection - latent infection

Question 10

Describe viral genomes

Answer 10

can compromise DNA or RNA
can be single or double stranded
genomes are smaller than host cells
range between 5000-230,000 base pairs

Question 11

What are the genome-based categories of viruses?

Answer 11

1. Double stranded DNA (dsDNA) viruses
   • Herpesviruses: herpes simplex, chicken pox, EBV
   • Papillomaviruses: warts (cervical cancer)
   • Poxviruses: small pox
2. Single stranded RNA (ssRNA) viruses
   Positive strand RNA viruses:
   • Picornoviruses: polio, rhinovirus (cold), hepatitis A
   Negative strand RNA viruses:
   • Rhabodoviruses: rabies
   • Orthomyxoviruses: influenza
3. Double stranded RNA (dsRNA) viruses
   • Reoviruses: reovirus, rotavirus (diarrhea)
4. Retroviruses (RNA viruses with DNA intermediates)
   • HIV: AIDS
   • HTLV-1: Leukaemias

Question 12

Describe viral replication: dsDNA virus

Answer 12

Viral genome must be transported to the nucleus

1. Viral DNA is transported to host nucleus
2. Host RNA polymerase converts viral DNA to viral mRNA in nucleus, then it is transported to cytoplasm
3. Viral RNAs are translated to new viral proteins, transported back to nucleus
4. Viral DNA is replicated by host DNA polymerase and viral factors
5. Viral genome and proteins reassemble, followed by release

Question 13

Describe viral replication: positive strand ssRNA virus

Answer 13

Viral genome can remain in the cytoplasm

1. Viral RNA (mRNA) is translated to proteins by cytoplasmic ribosomes
2. The viral RNA genome is replicated by the viral synthetase
3. Viral proteins form the capsid and encapsulate the replicated RNA genomes forming new virions
4. The new virions bud from the infected cell

Question 14

Describe Polio virus replication

Answer 14

Positive strand ssRNA virus
Vpg protein at 5’end and a polyA tail at 3’end

1. RNA acts as mRNA resulting in translation using host ribosomes
2. Large polyprotein is cleaved to produce 20 proteins including RNA polymerase.
3. RNA polymerase transcribes viral RNA to negative RNA strand
4. Acts as template for new positive RNA strand

Question 15

Describe viral replication: negative strand ssRNA virus

Influenza

Answer 15

1. Virus is endocytosed
2. RNA negative strand converts to mRNA(+) using viral RNA polymerase in the nucleus
3. RNA replication happens in the nucleus
4. mRNA is translated in cytoplasm to produce viral
   proteins (e.g. HA, NA, NP, RNA polymerase, M2 protein)

Question 16

Describe viral replication: dsRNA virus (Reovirus)

Answer 16

1. Late structural proteins assemble into developing
   inner core
2. Ten viral mRNA gene segments are inserted
   into inner core
3. Negative RNA strand is copied on viral mRNA to
   replicate dsRNA genome
4. Inner core used for:
   • mRNA transcription
   • Virion progeny production

Question 17

Describe viral Replication: Retrovirus (HIV)

Answer 17

1. Entrance via binding and fusion of viral envelope
   proteins to specific host cell receptors
2. Virion uncoating
3. The viral reverse transcriptase reverse transcribes one RNA strand into ssDNA and then into dsDNA. Enters nucleus.
4. The viral DNA integrates into host DNA, through the
   function of viral integrase. Provirus is formed.
5. Transcription of viral DNA to viral mRNA and progeny RNA.
6. Synthesis of HIV polyproteins
7. Processing of HIV-polyproteins by the the viral protease and generation of mature functional proteins
8. Encapsidation of viral ssRNA
9. Budding of virions
10. Release of virions

Question 18

What are bacteriophages?

Answer 18

Viruses that infect bacteria
(Mostly) dsDNA viruses
Among the most common and biodiverse entities on the planet
Found in soil, intestines, sea water…
In sea water: up to 9×108 virions/ml; up to 70% of marine bacteria
may be infected by phages
Applications
• Medicine
• Biology
• Anti-terrorism
Types
• Latent/temperate – Lambda (λ)
• Lytic – T4

Question 19

Describe bacteriophage structure

Answer 19

Nucleocapsid head
Capsid/ protein coat
Collar 
Sheath
Base plate
tail, tail spike and tail fibres

Question 20

Describe T4 bacteriophage life cycle - lytic phage

Answer 20

1. Attachment - the phage attaches to specific receptors on the cell wall of E. coli
2. Penetration - following attachment, phage DNA is injected into the bacterial cell, leaving the phage coat outside
3. Transcription - phage DNA is transcribed, producing phage mRNA, which is translated to phage proteins
4. Replication of phage DNA, Synthesis of proteins - phage coat proteins, other protein components and DNA are produced separately. Host DNA degraded
5. Assembly - phage components are assembled into mature virions
6. Release - the bacterial cell lyses and releases many infective phage

Question 21

Describe λ bacteriophage life cycle – temperate phage

Answer 21

1. Attachment
2. Linear phage DNA
   circularizes
3. Replication (lytic)
   or
4. Integration (lysogenic) - prophage is integrated into bacterial chromosome
   • Excision/Replication
5. New virions formed
6. Cell lyses releasing phage virions