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Viruses
Viruses are highly diverse, and yet possess many common features. All drift
through their environment, ending up on target cells by chance. Once their genome
has been internalised, the nucleic acid is converted into +sense mRNA to be
translated. The genome structure itself varies greatly between viruses: it can be
composed of DNA or RNA, and may be double or single stranded. Furthermore the
ssRNA may be + or – sense.
Influenza A – Negative sense single stranded RNA
 The particle is 80-120nm in diameter, and is encapsulated, with an overall
spherical structure.
 Its genome is composed of –ve sense ssRNA, split into 8 separate strands.
Each strand codes for 1 or 2 proteins. For example segment 1 encodes
hemagglutinin, which mediates binding to target cells, while segment 2
encodes neuraminidase, a protein involved in releasing progeny viruses from
infected cells.
 After transcription into +ve sense mRNA, a virus encoded nuclease cleaves 5’
7-methyguanosine caps off host mRNA, and uses these as primers for some
of the virus transcripts. This makes virus mRNA with 5’ caps on the end, ready
to be translated by the host cell ribosomes.
 Shuffling of the 8 different RNA strands between virions in simultaneously
infected cells can produce new, highly infectious hybrids. Major cause of
pandemics and zoonoses.
 New virions are released by budding, and pick up a lipid bilayer envelope in
doing so. The virus also eventually causes the cell to lyse, releasing many
virus particles which can go on to infect neighbouring cells.
 The most infamous epidemic was in 1918, when H1N1 killed 40m. Its lethality
was due to the fact that it triggered a cytokine storm: a positive feedback
loop as cytokines (signalling proteins) activate T cells and macrophages,
which then produce more cytokines. This causes severe lung damage and
death.
HIV – Positive sense single stranded RNA virus
 Lentivirus (slow replicating retrovirus). Spherical, 120nm in diameter.
 +ve sense ssRNA which encodes 9 genes, enclosed by a capsid made of 2000
copies of viral p24 protein.
 The RNA is tightly bound to the nucleocapsid protein p7, as well as enzymes
including reverse transcriptase, proteases, ribonuclease and integrase.
 A matrix of p17 protein surrounds the capsid, ensuring the integrigty of the
particle, and the whole thing is surrounded by an envelope formed during
budding from the phospholipid bilayer.
 HIV infects several cell types, perhaps most significantly CD4+ T lymphocytes.
Viral particles adsorb to the receptor CD4, binding via the HIV envelope
protein gp120. Interaction with a second receptor, usually a chemokine
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receptor, causes virus-cell fusion. The genome is released into the cytoplasm,
and reverse transcription synthesises cDNA. This is converted to dsDNA, to be
integrated into the host cell chromosome. This ‘provirus’ is transcribed and
translated with host cell machinery to make new virion particles.
Virions are assembled in the cytoplasm and bud from the membrane. They
only become infectious following processing by a protease (they have used
polyproteins to increase genome efficiency). The HIV protease has been the
target of some antiviral drugs.
By directly damaging CD4+ cells, as well as triggering apoptosis in unaffected
bystander cells and also stimulating their attack by CD8 cytotoxic
lymphocytes, the immune system becomes weakened. Below a critical
threshold, cell-mediated immunity is lost – this is AIDS.
Hepatitis B (and the Delta Agent) – Good example of space efficiency
 From the hepadnavirus family. One of the smallest viral genomes known, at
just 3200bp. Amazingly, every single base is part of a codon for at least one
gene.
 DNA genome is partially double-stranded (made up of several strands that
overlap substantially) and is circular. The genes within it overlap too to
maximise space efficiency.
 They affect liver cells, in which they trigger a strong immune response
involving cytotoxic T cells mainly, which then damage the liver tissue.
 This pathogen is itself parasitised by another ‘subvirus’ called the delta
agent. This has circular –ve sense RNA genome of 1679 bases. The delta
agent relies upon hepatitis B to produce the proteins needed for its coat.
 Its genome encodes an RNA binding protein, but it can also act as ribozyme,
cleaving itself. It may well be a relict from the RNA world.
T4 Bacteriophage
 Functions like a syringe, injecting its genome into the cell.
 Binding to the surface of an E. coli cell triggers a conformational change in
the viral gp18 protein.
 This contracts the outer tube, driving the inner tube (a hollow spike) into the
cytoplasm. The DNA genome is then injected into the cell under pressure,
where it is replicated and transcribed/translated by host cell machinery.
 New virions are assembled (in the case of T4) with helper proteins, with the
base plate assembled first and then the tails added. The head spontaneously
assembles and attaches afterwards. The whole process take around 15mins.
 In the lytic cycle, the viral enzyme endolysin breaks down the peptidoglycan
cell wall, lysing the cell, releasing many phage particles.
 In the lysogenic cycle, the viral genome is integrated into the host genome –
it has become a ‘prophage’. This does not kill the cell, and it may be a long
term resident.