Introduction to Virology

In the past, viruses were only classed based on the diseases they caused (their tropisms). However different viruses may have similar tropisms and similar viruses can have different tropisms.

Respiratory viruses eg influenza, rhinovirus and adenovirus are usually acquired by droplet inhalation and replicate in the respiratory tract. Enteric viruses such as polio, rotaviruses, reoviruses and some adenoviruses replicate in the gut and cause gastric infection. They’re acquired by ingestion of faecal-contaminated material. Arboviruses such as flaviruses, bunyaviruses and some rhabdoviruses infect insects which go on to ingest vertebrate blood. They replicate in insect tissue and are transmitted to the vertebrate host. Hepatitis viruses = all viruses which cause liver disease. Sexually transmitted viruses include herpes simplex and papilloma viruses.

Viruses only replicate in certain cell types or in whole organisms the virus has a tropism for, as they are obligate intracellular parasites. Bacterial viruses are easiest to grow so are often used as model systems. Animal viruses as well as some plant viruses can be cultured in tissue or cell cultures. Plant viruses are typically most difficult to grow as study often requires growth of whole plant.

Titer = number of infectious units per volume of fluid.

One way of measuring viral infectivity is to carry out a plaque assay. Plaques are clear zones which develop on lawns of host cells, which can be either bacterial or tissue culture. Different tissue samples can be tested to find the tropism of the virus. Each plaque results from infection by a single virus particle.

The capsid is formed from structural subunits and large assemblies are referred to as capsomers. They are highly symmetrical in arrangement of structural subunits, showing either helical or icosahedral symmetry. Bacteriophages are an example of a ‘complex’ virus, as they have an icosahedral head and helical tail. Most mammalian viruses exhibit icosahedral symmetry, with 20 sides and 12 vertices.

Viruses may be naked (no membrane) or enveloped (have a membrane). Virion structure is diverse, with many different shapes, chemical compositions and sizes ranging from 0.018 to 0.3 μm.

Virion = nucleic acid packaged into a protein coat known as a capsid.

Nucleocapsid = nucleic acid and protein packaged into a virus

Some virions contain enzymes critical to infection such as lysozymes, nucleic acid polymerases and neuraminidases. Lysozymes make a hole in the cell wall and lyse bacterial cells. Neuraminidases are enzymes which cleave glycosidic bonds, allowing liberation of viruses from the cell.

The Baltimore classification of viruses uses roman numerals to classify viruses based on their genetic make up.

Class I = dsDNA (most bacteriophages, herpesviruses and poxviruses)

Class II = ssDNA (+) sense eg parvoviruses

Class III = dsRNA eg reoviruses

Class IV = ssRNA (+) sense RNA eg picomaviruses and coronaviruses

Class V = ssRNA (-) sense RNA eg rhabdviruses and influenza viruses

Class VI = ssRNA (+) sense with dsDNA intermediate eg retroviruses

Class VII = dsDNA with RNA intermediate eg hepadnaviruses

The initiation/early phase of virus replication involves recognition, attachment, penetration and uncoating. Penetration and uncoating are also classed as part of the eclipse period.

Recognition and attachment involve target cell receptors and viral attachment proteins. The target cell receptors may be proteins, carbohydrates, glycoproteins or glycolipids. The viral attachment protein may be capsid, a protein that extends from the capsid, or glycoproteins for enveloped viruses. The virion often changes structure when it binds its receptor, exposing hydrophobic amino acids so it can penetrate and cross the host cell membrane.

Pore-mediated penetration, also known as viropexis, only occurs in naked viruses. This means the virus attaches to the cell and ejects its genome into the cytoplasm of the host cell.

Both naked and enveloped viruses may carry out penetration and uncoating via endocytosis.

Only enveloped viruses can carry out penetration and uncoating by membrane fusion.

Eclipse period = virus penetrating and entering the cell, the capsid is no longer present.

The replication stage, which is an overlap between the eclipse period and late phase, involves transcription, protein synthesis, genome replication and assembly. Nucleic acid polymerases present in all organisms are DNA dependent RNA polymerase and DNA dependent DNA polymerase. Virus-specific nucleic acid polymerases are RNA dependent RNA polymerase and RNA dependent DNA polymerase. RNA dependent DNA polymerases are reverse transcriptases.

Smaller DNA viruses are more dependent on the host cell for replication so many viruses promote cell growth. Other than for poxviruses, transcription occurs in the nucleus. Transcription is regulated by the interaction of DNA binding proteins with regions of the viral genome. The viral regulatory regions are similar to the host’s. mRNA for non-structural proteins (early proteins) is transcribed first and genome replication initiates transcription of late genes. DNA replication semi conservative.

Genome replication and transcription are similar for RNA viruses. A dsRNA replicative intermediate is always formed. dsRNA alerts the host immune system to viral infection as it shouldn’t be present. Polymerases must be virally encoded. Other than influenza, replication occurs in cytoplasm. RNA viruses are more prone to mutation due to reduced genome stability.

Translation of viral mRNA is dependent on host cell functions, as viruses are unable to turn genes on and off. Eukaryotic ribosomes can’t translate polycistronic mRNA, and viruses promote preferential translation of their mRNA. Post-translational modification may occur. Viral assembly is essentially a crystalline process.

There are 3 main methods of viral release. Naked viruses usually lyse the host cell whereas enveloped viruses tend to bud away from the host cell surface. Both naked and enveloped viruses may also be released by exocytosis.