Viruses - intro

History of the study of viruses

Originally only distinguished by size

Name came from ‘filterable virus’ as they were smaller than bacteria so passed through their filters

Was a flaky definition as small organisms like mycoplasmas would have been included as viruses, and not giant viruses like Mimivirus

What breakthroughs furthered study of viruses

Electron microscope

First x-ray diffraction images

Genome identification of viruses → led to global taxonomy

Important features of viruses

Metabolically inert (rely on host cell for energy, metabolic intermediates, and protein synthesis)

Obligate intracellular parasites (can only replicate in host cells)

Have own genome

Usually have protein shell protecting its genetic elements (capsid)

Some have outer lipid envelope

When outside cell known as ‘virion’ - can move from one cell to another

Structure of viruses - difference between those that infect eukaryotic vs. prokaryotic cells

Capsid formed of protein subunits and packed with DNA

Viruses that infect eukaryotic cells - most often enveloped with protein lipid shell, allows attachment to and mechanism of entering cell

Viruses that infect prokaryotic cells - usually have no shell, some have mechanisms to inject DNA into host cell

Simplified virus life cycle

Attachment

Penetration - cell engulfs virus via endocytosis / injection of viral material

Un-coating - viral contents released

Biosynthesis - viral DNA enters nucleus and is replicated using cell machinery

Assembly - new phage particles assembled

Release

Variety in length of viral genomes

From around 1.7k to 2.5 million base pairs (Pandoravirus)

Mutation rate of viruses vs. mammals and bacteria

Higher mutation rate

What is the Baltimore classification

Developed in 1971

Based on the route of information transmission from genome to mRNA (from which the viral proteins are translated)

Divided into classes I to VII

Classes III to VII require RNA replication, and therefore need to encode RdRp or reverse transcriptase which is error prone

What are virus hallmark genes and what are their use

Encode proteins involved in central functions of viral replication and morphogenesis

Present in diverse number of viruses

Can use phylogenies of VHGs to construct evolutionary models of viral genomes

What are examples of animal viruses

SARS-Cov-2

Influenza A and B

Features of SARS-Cov-2

Single genome

New diversity generated by mutation and recombination

Have ‘coronas’ to bind to host cells, and are the targets of antibodies

Most likely originated in bats

Life cycle of of SARS-Cov-2

Binds to receptor, fusion to gain entry, genomic RNA translated for viral replication proteins, viral RNA replicated, virions assembled and released

SARS-Cov-2 concern variants

Came from mutations in the spike gene that allowed better binding to host cells and evading antibodies

Variants developed in surveilled populations, in wildlife that then spilled back to humans, and from chronic infection where treatment caused rapid evolution

Features of influenza A and B

Eight genome segments

Diversity/new strains caused by: antigenic drift (mutations) or antigenic shift (reassortment, where two viruses enter the same cell and mix segments - creating new subtype)

What is an example of a plant virus, and what type of virus is it

Faba bean necrotic stunt virus - transmitted by aphids

It’s a multipartite virus - each gene segment is packed into a different virion, all virions need to infect the plant for the virus to be effective

Theories for multipartite infection

Seemingly have an evolutionary disadvantage of needing simultaneous infection

May have evolved due to ability to quickly change levels of gene expression and adapt in rapidly changing environments

Potentially higher number of infections

What are viruses that infect bacteria called

Bacteriophages

Example of a bacteriophage

Lambda phage (also a specialised transducing phage)

Infects E. coli - can switch between lysogenic and lytic cycle either spontaneously or induced by stimuli. Lysogenic cycle preferred when host abundance is low, and lytic when host bacteria can proliferate and reach high density

Chronic - so the phage is released continuously without killing the cell

What is the use of phage therapy

Can be used to combat antibiotic resistance, using phages instead of antibiotics

Can also employ phages to select for bacteria that are more sensitive to antibiotics - use phages that have antibiotic efflux pumps as receptors to select for bacterial mutants that are phage-resistant due to impaired pumps

Or phages can select for bacterial mutants that are phage-resistant as they lack a capsule, therefore less virulent

Two types of viruses that are dependent on other viruses

Virophages and satellite viruses

Features of virophages

First discovered in 2008

Requires co-infection with a giant virus (usually a mimivirus member)

Virophage replicates inside the giant virus’s viral factory, reducing the giant virus’s replication

Features of satellite viruses (and example)

Requires co-infection with a helper virus

E.g. Hep D requires the infection of Hep B which provides the envelope proteins. Co-infection makes the Hep B infection more severe - more rapid progression to cirrhosis and higher rates of cancer