Key principles regarding virus-host interactions:
Host cells can be permissive or non-permissive (or semi-permissive).
Permissive cells provide the necessary receptors, biochemical pathways, and other factors that support viral replication.
Viruses have evolved to take advantage of these naturally occurring features of host cells.
Viruses reprogram host cells to promote their own entry, and they highjack the molecular machinery for replication, and, in some cases, activation and other viral functions.
Interactions between the host and virus determine the severity and duration of infection and the development of disease.
Types of Cellular Infections:
Failed, aka, abortive
The virus does not replicate and there are little to no effects on the cell.
Cytolytic
Viral replication and cell takeover result in cell death.
Persistent infections
Viral nucleic acids remain in at least some host cells.
Chronic infections, in which the virus is replicating, or productive.
Persistent infection can be latent, in which the virus is not productive.
Slow, in which there is a long incubation period followed by progressive disease.
Be aware that viruses can be present in different states (chronic, latent, slow) in different cells within the same host.
Recurrent
Periods of latent infection that alternate with periods of active virus production.
Oncogenic
Transformation or immortalization of host cells occur.
An example of this is type of infection is human T-cell lymphotropic virus 1.
Key steps in the process of viral infection
Keep in mind that we'll show a generalized representation, and that viruses use a variety of mechanisms to enter, replicate, and disseminate within their hosts.
Entry
For example, show that many viruses enter the host's respiratory tract via inhalation. Other common entry portals are the gastrointestinal and urogenital tracts, mucous membranes, and breaks in the skin.
Primary Replication
Occurs near the site of entry.
In our example, primary replication occurs in the oral cavity and upper respiratory tract.
Replication can occur in host macrophages.
Dissemination
Spread from the primary replication site occurs via the circulatory system.
Viremia means viruses are present in the blood.
Viruses can also travel in the
lymphatic and nervous systems.
Virions may travel freely or associated with lymphocytes and macrophages.
Secondary Replication
Upon dissemination, secondary replication can occur.
For example, show that viruses can continue to replicate in macrophages, the liver, and endothelial vessel linings.
Secondary viremia
Delivers the virus to the target organs.
Target organs
Viruses can cause cell damage and disease in muscles, skin, kidneys, and the central nervous system.
Persistence in the target organs may be established.
The virus is shed into the environment, often via the respiratory, gastrointestinal, or urogenital tracts.
Tropism for target organs depends on various factors, including: the presence of host cell receptors, biochemical requirements, temperature, and pH.
Virions can "surf" along the surface of cell membranes to reach their entry locations.
Within host cells, virions interact with the
microtubule networks to travel to their replication and exit sites.
Between cells, virions use "virological synapses," which are temporary tight junctions between infected and uninfected host cells; they can use membrane fusion between adjacent cells; or, the virions can move freely.
Host defense to viral infection
Fever can be effective against viruses that replicate within a narrow temperature range.
Inflammation contributes to increases in temperature, produces acids, and generally alters host biochemistry.
Interferons inhibit viral replication.
Adaptive immunity, which consists of anti-viral
T-cells, B-cells, and
antibodies, attempt to eradicate the virus.
Key determinants of viral pathogenesis
Can the virus invade, spread, and replicate within the host?
If it cannot, then pathogenesis will be non-existent or limited.
Virus morphology and tropism are important factors in this.
Is the virus cytopathic, and, if so, how cytopathic?
Cytopathic effects are the result of competition for host resources, and can take several forms, including:
- Inhibition of cell protein synthesis
- Inhibition or degradation of cell DNA
- Alterations to the cell membrane or cytoskeletal structures
- Formation of multinucleated syncytia
- Formation of inclusion bodies
- Production of toxic substances
In the illustration, we see cells infected with a herpes simplex virus. Notice the morphological changes induced by cytopathic effects: rounded cells, multinucleated nuclei, and inclusion bodies.
Is the host's immune response self-damaging?
In other words, is the host causing too much harm to itself in the process of trying to eradicate the viral infection?
Some examples of this include:
- Formation of immune complexes
- Development of autoimmunity
- Cytokine storms
- Immune suppression
A key clinical takeaway:
Less virulent strains cause less damage to the host, but, in keeping the host alive, the virus continues to steal host resources for replication and enhances its own reproductive fitness. Thus, natural selection often favors these strains.
