Core Virology – Virus Structure and Classification
Posted On May 31, 2018
1. Virus Structure
Viruses are obligate intracellular organisms – this means they need to reside inside a host cell to survive. They are very small, ranging from 18 to 230 nm, making them the smallest infectious agent out there. To visualise their shape and structure, electron microscopy can be very useful.
To put this into perspective, I found a great tool created by learn.genetics.utah.edu, which shows you just how big different cells are compared to things such as a grain of rice and a coffee bean. Check it out here!
Viruses have two components that they all share, but the structure of which varies. These are their nucleic acid and their capsid, the combination of which is called a nucleocapsid. Some viruses have additional structures, such as an envelope or a tegument, but this will be discussed in more detail in the case of specific examples of viruses.
1.1 – Viral Genome
Viruses can have two main types of genome: DNA and RNA, and each of these are very different. RNA viruses need their own RNA polymerase to copy their genome as there is no equivalent enzyme in the host. This is called an RNA dependent RNA polymerase. These enzymes are very error prone as they have no proof-reading capabilities. This means that RNA viruses are more variable and can evolve rapidly if needed. There are therefore usually many different subtypes and serotypes of RNA viruses, they are often zoonotic and they can usually adapt to evade the host’s immune system.
Viral genomes can be circular or linear, and this is not correlated with the shape of type of nucleic acid. Linear genomes can be segmented, meaning it is divided into several parts. These characteristics vary greatly between viruses, so will be explored in more detail when specific examples are mentioned.
1.2 – Viral Capsid
The capsid of a virus is the protein shell of a virus. There are three main types: icosahedral, helical and complex. Most viruses which cause disease in vertebrates have an icosahedral capsid.
a) Icosahedral Capsid
This shape has 12 vertices, 20 triangular sides and is composed of pentagonal capsomeres at the vertices and hexagonal capsomeres at the faces (pentons and hexons). The triangulation number (T=X) is a way of determining the size and structure of a virus capsid. I found this concept quite tricky to get a grasp of, so here is a video that I found which helped me understand the principle behind it.
Examples: parvoviridae, adenoviridae…
b) Helical Capsid
These capsids are in a spiral-like configuration, where single capsid proteins are arranged as a helix. All animal viruses with a capsid of this shape are enveloped.
Examples: paramyxoviridae, rhabdoviridae
c) Complex Capsid
Some of the large viruses have capsids with more complex structures than those previously mentioned. The illustration shown in the figure above is just one example of what a complex capsid may look like.
1.3 – Virus Particles
Virus particles are functional nanomachines. They protect viral nucleic acid from degradation when outside the cell, function as a machine to deliver the viral nucleic acid to an uninfected cell, act as a vehicle for the transport of virus from one host cell to the next and from one host to the next. They are a major factor in determining the tropism of the virus inside a host (i.e. which cells they can infect). Some particles also protect viral nucleic acid from detection and/or degradation when inside a host cell and act as a machine for the efficient replication or transcription of the viral genome.
Viral proteins can be separated into two categories: structural and non-structural. Structural proteins are everything needed for the structure of the protein, and non-structural can have various roles such as proteases, helicases, RNA dependant RNA polymerase, primers for replication, etc. They can help the virus evade the host immune response or could be its targets. These proteins are made in the infected cell after infection.
1.4 – Virus Envelope
Some viruses contain lipid bilayer which is derived from the host plasma membrane, and is acquired when the virus leaves a host cell. It contains glycoproteins, and can carry receptors to help with cell entry and antigenic determinants which are recognised by antibodies. A virus’ envelope is specific to the type of virus it is.
Enveloped viruses are more likely to have an irregular shape and are more fragile than viruses with just a capsid. They are more easily lysed by detergents, disinfectants and the outside environment. They must stay wet, and cannot survive in the gastrointestinal tract. They are not easily spread and mostly cause persistent infections.
Non-enveloped viruses are more environmentally stable, are resistant to detergents, are able to dry out and still retain infectivity. They can survive adverse conditions in the gut and can be spread easily. They are mostly released from infected cells by budding and cause acute infections.
2. Virus Classification
There are many different types of viruses, and many ways of classifying these. The most common classification techniques are taxonomic and the Baltimore classification, which sorts viruses depending on their genome structure and the way in which they replicate.
2.1 – Taxonomic Classification
Only 5 levels of taxonomic classification are specified by the International Committee on Taxonomy of Viruses (ICTV). There is no requirement to use all these levels in virus taxonomy. It is therefore possible for a virus to be assigned to a family or order, but not assigned to a genus. Also, not all viruses are assigned to a particular order.
The viral genome can vary depending on the virus. Human cells have double stranded DNA, and replicate via a single stranded RNA. Viruses however are not so simple, as they can be either DNA or RNA viruses, but each can also be single- or double-stranded. The structure of a viruses’ genome determines how it will replicate, and this is the basis of the Baltimore Classification.
The figure below is the basis of this classification. It is first divided in two depending on how the virus replicates: with or without reverse transcriptase. Then, for viruses that replicate without reverse transcriptase (RT) further segregation is made depending on whether the genome is made up of DNA or RNA, then whether it is double-stranded or single-stranded. The replication of the viruses within these groups is similar, and will be discussed in a future post.
Baltimore Class I: These are double-stranded DNA viruses, and replicate by taking over host cell machinery. Many of them are cryptic, meaning that they often halt their cycle and hide in the cell until host proteins replicate, when they then resume their lifecycle and hijack host-cell machinery. Class I viruses usually have large genomes and replicate in the nucleus. Examples: herpesviridae, poxviridae, papillomaviridae…
Baltimore Class II: These are single-stranded DNA viruses which have a relatively small genome. They are usually non-enveloped and replicate in the nucleus using a double-stranded DNA intermediate, via a rolling circle mechanism. Examples: circoviridae, pravoviridae…
Baltimore Class III: These are double-stranded RNA viruses. They replicate inside their capsid in the cytoplasm of the infected cell. They need their own RNA polymerase to copy their genome as there is no equivalent in the host cell. This is a RNA-dependant RNA polymerase. Examples: Reoviridae, Birnaviridae…
Baltimore Class IV: These are positive sense single stranded RNA viruses. Positive sense is a reference to translation – it indicates that the virus genome can be directly translated by host ribosome to create virus proteins. Replication usually occurs in the cytoplasm. Examples: Flaviviridae, Coronaviridae, Picornaviridae…
Baltimore Class V: These are negative sense single stranded RNA viruses. Negative sense indicates that the virus genome cannot be directly translated to create proteins, they must first be transcribed by viral polymerases. Replication usually occurs in the nucleus. Examples: Orthomyxoviridae, Paramyxoviridaw, Bunyaviridae, Filoviridae, Rhabdoviridae…
Baltimore Class VI: These are positive sense single stranded RNA viruses that require to be reverse transcribed before replication. This means that they are made into double stranded DNA first by virus-encoded proteins and then incorporated into the host genome. The viral genome is then replicated along-side the host genome. Examples: Retroviridae (HIV)
Baltimore Class VII: These are double stranded DNA viruses that require to be reverse transcribed before replication. These viruses replicate using a double-stranded RNA intermediate, then a dsDNA intermediate that is integrated into the host genome and replicated by the host, similar to class VI viruses. Examples: Pararetroviridae, Hepadnaviridae
2.3 – Other Classification Systems
a) The Holmes Classification
The Holmes classification classifies viruses into three groups within the order Virales
Group I: Phaginae – attack bacteria
Group II: Phytophaginae – attack plants
Group III: Zoophaginae – attack animals
b) The LHT System of Virus Classification
This system is based on chemical and physical properties of the virus, such as nucleic acid, capsid type, presence or absence of envelope, triangulation number etc.