Anti-Viral Defences


  Viruses are unable to multiply on their own. They depend on the body's own cells.

  To multiply, a virus must first enter the body. One of the ways it does this is through the mucous membranes of the gut or respiratory system. Some viruses spread in the blood around the body. They are not able to infect cells indiscriminately, because they can only attach to cells expressing particular receptor groups on their surfaces.

  When a virus encounters such a cell, it binds using a complementary group.

  The virus is now able to penetrate the cell. The capsid, the part of the virus containing the foreign genetic material, enters the cytoplasm.

  There it breaks down, releasing nucleic acid into the cell. It is important to remember that viruses can carry either RNA or DNA in single or double stranded forms.

  Many viruses replicate in the cytoplasm where the biomolecules it codes for are synthesised. These include more viral nucleic acid , protein and glyco-proteins for the viral envelope if there is one, and viral surface receptors. As a side effect it may also cause the cell to produce additional host antigens on the cell surface. Some viruses incorporate their DNA into the nuclei.

  The components of the virus assemble in the cytoplasm and at the cell membrane. Viral receptor proteins protrude through the plasma membrane, and within the cytoplasm viral nucleic acids associate with capsid proteins to form a new capsid. The plasma membrane buds off to enclose this new capsid, causing a new virion to be released into the body. Many virions are produced simultaneously in each cell and the virus proliferates.

  Each released virion is capable of infecting another cell. Neighbouring cells in the body are likely to be of the same type, and since the virus targets cells expressing specific host receptors on their surfaces, propagation of the infection is rapid.

  The immune system has several defence mechanisms against viral infection. Here, a virus binds to its target cell.

  As we saw, it fuses with the host cell, and releases its genetic material into the cytoplasm.

 When the foreign genetic material enters the cell and starts to synthesise viral products, the cell is stimulated to make alpha and beta interferons.

  These interferons can signal to neighbouring cells to directly inhibit viral metabolism. They do this by binding to interferon receptors which signals the synthesis of anti-viral proteins. The anti-viral proteins can switch the cell into a virus resistant state if it should become infected. Interferon gamma produced by activated T-cells also induces synthesis of MHC class I molecules, which make the cell more readily recognised by cyto-toxic T-cells.

  When a virus infects the activated neighbouring cell, the anti-viral proteins detect foreign genetic material and block viral replication by breaking down the mRNA and stopping protein synthesis.

  These proteins put the cell into stasis, which limits further replication of the virus and spread of infection.

  This holding action gives the immune system time to mobilise the T-cell response.

  One consequence of interferon signalling is an increased production of major histocompatibility molecules, particularly class I. This is synthesised within the endoplasmic reticulum, where it comes into contact with peptide fragments of all the proteins present in the cell.

  All of the proteins are sampled by binding to MHC class I, which carries it to the cell surface. This includes any viral peptides synthesised by the cell.

  T-cells that have been educated within the thymus will recognise and bind to a receptor composed of MHC class I, plus non-self protein peptide. It does this through its T-cell receptor and CD8 molecules.

 Once attached there may be a direct inter-action between the CD95 ligand group of the T-cell, and a CD95 receptor on the target, infected cell. An indirect signal may also be sent using, tumour necrosis factor, or lymphotoxin, to a tumour necrosis factor receptor on the target cell.

  In either case, this triggers the release of agents within the cell which disrupt nuclear DNA, and cause cell death by apoptosis. The cytotoxic T-cell is now free to seek other similarly infected cells.

 The body's other defence mechanism is carried out by free immunoglobulin. Both infected cells and free virus present viral proteins on their surface.

   Antibodies can bind to viral proteins expressed on the surface of infected host cells. In this case they signal to components of the complement system, which attack the cell membrane and damage the cell by membrane attack complexes.

  The same antibodies on encountering a virion, can also bind to its antigens, making it unable to attach to and enter uninfected cells.53Cbb>