MicrobiologyBytes: Virology: Pathogenesis Updated: October 19, 2004 Search

Virus Pathogenesis

Virus pathogenesis is an abnormal situation of no value to the virus - the vast majority of virus infections are sub-clinical, i.e. asymptomatic.

For pathogenic viruses, there are a number of critical stages in replication which determine the nature of the disease they produce:

1) Entry into the Host

The first stage in any virus infection, irrespective of whether the virus is pathogenic or not. In the case of pathogenic infections, the site of entry can influence the disease symptoms produced. Infection can occur via:

2) Primary Replication

Having gained entry to a potential host, the virus must initiate an infection by entering a susceptible cell. This frequently determines whether the infection will remain localized at the site of entry or spread to become a systemic infection, e.g:

Localized Infections:
Virus: Primary Replication:
Rhinoviruses U.R.T.
Rotaviruses Intestinal epithelium
Papillomaviruses Epidermis
Systemic Infections:
Virus: Primary Replication: Secondary Replication:
Enteroviruses Intestinal epithelium Lymphoid tissues, C.N.S.
Herpesviruses Oropharynx or G.U.tract Lymphoid cells, C.N.S.

3) Spread Throughout the Host

Apart from direct cell-cell contact, there are 2 main mechanisms for spread throughout the host:

Virus may get into the bloodstream by direct inoculation - e.g. Arthropod vectors, blood transfusion or I.V. drug abuse. The virus may travel free in the plasma (Togaviruses, Enteroviruses), or in association with red cells (Orbiviruses), platelets (HSV), lymphocytes (EBV, CMV) or monocytes (Lentiviruses). Primary viraemia usually proceeds and is necessary for spread to the blood stream, followed by more generalized, higher titre secondary viraemia as the virus reaches other target tissues or replicates directly in blood cells.

As above, spread to nervous system is preceded by primary viraemia. In some cases, spread occurs directly by contact with neurons at the primary site of infection, in other cases via the bloodstream. Once in peripheral nerves, the virus can spread to the CNS by axonal transport along neurons (classic - HSV). Viruses can cross synaptic junctions since these frequently contain virus receptors, allowing the virus to jump from one cell to another.

4) Cell/Tissue Tropism

Tropism - the ability of a virus to replicate in particular cells or tissues - is controlled partly by the route of infection but largely by the interaction of a virus attachment protein (V.A.P.) with a specific receptor molecule on the surface of a cell, and has considerable effect on pathogenesis. Many V.A.P.'s and virus receptors are now known.

5) Host Immune Response

Discussed elsewhere - obviously has a major impact on the outcome of an infection.

6) Secondary Replication

Occurs in systemic infections when a virus reaches other tissues in which it is capable of replication, e.g. Poliovirus (gut epithelium - neurons in brain & spinal cord) or Lentiviruses (macrophages - CNS + many other tissues). If a virus can be prevented from reaching tissues where secondary replication can occur, generally no disease results.

7) Cell/Tissue Damage

Viruses may replicate widely throughout the body without any disease symptoms if they do not cause significant cell damage or death. Retroviruses do not generally cause cell death, being released from the cell by budding rather than by cell lysis, and cause persistent infections, even being passed vertically to offspring if they infect the germ line. (All vertebrate genomes including humans are stuffed with retrovirus genomes which have been with us for millions of years). Conversely, Picornaviruses cause lysis and death of the cells in which they replicate, leading to fever and increased mucus secretion in the case of Rhinoviruses, paralysis or death (usually due to respiratory failure) for Poliovirus.

8) Persistence vs. Clearance

The eventual outcome of any virus infection depends on a balance between two processes:

i) Persistence:

Long term persistence of virus results from two main mechanisms:

a) Regulation of lytic potential

The strategy followed is the continued survival of a critical number of virus infected cells - sufficient to continue the infection without killing the host.

b) Evasion of immune surveillance

Includes:

ii) Clearance:

Example - Influenza virus:

2 mechanisms allow influenza virus to alter its antigenic constitution:


© MicrobiologyBytes 2004.