Abnormal Replication and Viral Interference
Two reasons for abnormal replication
| The reason lies in… | Which gives… |
|---|---|
| The virus — defective viruses | §2 |
| The host cell — non-permissive cells | abortive infection, §3 |
That two-way split is worth memorising as the frame for the whole unit: replication can fail because the virus is incomplete, or because the cell is inadequate.
- Name the two reasons for abnormal replication. → The virus — defective viruses; and the host cell — non-permissive cells, giving abortive infection
⭐ Defective viruses ★★★
Viruses that are genetically deficient and incapable of producing infectious progeny virions. They lack the gene or genes necessary for a complete infectious cycle.
A virus that can supplement the genetic deficiency and make defective viruses replicate progeny virions, when it simultaneously infects the host cell with the defective virus. Example: AAV (adeno-associated virus) and adenovirus.
Defective viruses that can occupy host cell materials so as to interfere with normal viral replication.
For the remaining marks, give both of the things that can happen to it:
1 · It can be rescued by a HELPER VIRUS, which supplies the missing function when it co-infects the same cell, allowing progeny virions to be produced. The classic pair is AAV with adenovirus. HDV (hepatitis D) with HBV as its helper is the clinical example — see the Hepatitis unit.
2 · It can act as a DIP — a defective interfering particle — occupying host cell materials and thereby interfering with the replication of normal virus. That links this term directly to §4.
Note the contrast the examiner may be probing: a defective virus fails because of the virus; an abortive infection fails because of the cell.
The abstract definition has one famous patient-facing consequence.
HDV cannot make its own envelope. It uses HBsAg — the surface antigen of hepatitis B — so it can only infect someone who also has HBV. HBV is its helper virus.
Two scenarios follow, and they are not equivalent:
Co-infection — both acquired together. Usually resolves, because clearing HBV clears HDV with it.
Superinfection — HDV arriving in a chronic HBV carrier. Severe, often fulminant, and usually chronic, because the helper is permanently present.
And the elegant consequence: vaccinating against hepatitis B also prevents hepatitis D. Remove the helper and the defective virus cannot exist.
- Define a defective virus. → A genetically deficient virus, lacking genes needed for a complete infectious cycle, and incapable of producing infectious progeny
- Define a helper virus. → A virus that supplements the genetic deficiency and lets the defective virus produce progeny when both infect the same cell — e.g. adenovirus for AAV
- Define a DIP. → A defective interfering particle — a defective virus that occupies host cell materials and interferes with normal viral replication
- Give the clinical example. → HDV is defective and uses HBsAg from HBV as its helper — so the hepatitis B vaccine also prevents hepatitis D
Non-permissive cells and abortive infection ★★★
A host cell that cannot provide the conditions for viral replication. A permissive cell is one that can.
A virus infection which does not produce infectious progeny, because the host cell cannot provide the enzyme, energy or materials required for viral replication.
Both end with no infectious progeny. The examiner's question is always whose fault was it?
Defective virus — the virus is missing a gene. Put it in a perfectly good cell and nothing happens. Rescue it with a helper virus.
Abortive infection — the virus is complete and the cell is inadequate; it lacks the enzyme, energy or materials. Put the same virus in a permissive cell and it replicates normally.
One is a defect of the genome; the other is a defect of the environment.
Note also that abortive infection is another face of §5 of the previous unit: tissue tropism is not only about which cells the virus can enter, but about which cells can support it once it is inside.
- Define a non-permissive cell. → A host cell that cannot provide the conditions for viral replication
- Define abortive infection. → An infection producing no infectious progeny, because the host cell cannot supply the enzyme, energy or materials needed
- How does it differ from a defective virus? → Abortive infection is the cell's inadequacy; a defective virus is the virus's own genetic deficiency
⭐ Viral interference ★★★
When two viruses simultaneously infect one host cell, one virus may inhibit the replication of the other.
Range of occurrence
- Between different species of viruses
- Between the same species of viruses
- Between inactivated viruses and live viruses
⭐ The three main mechanisms
| Mechanism | Detail |
|---|---|
| a | One type of virus inhibits the subsequent adsorption and penetration of another virus, by blocking or destroying receptors on the host cell |
| b | Competition of the two viruses for replication materials — e.g. receptors, polymerase, translation initiation factors |
| c | One type of virus may induce the infected host cell to produce INTERFERON, which prevents viral replication |
⭐ Medical significance
| Detail | |
|---|---|
| Advantage | a. Stops viral replication and leads to patient recovery. b. Inactivated virus or live attenuated virus can be used as a VACCINE to interfere with infection by the virulent virus |
| Disadvantage | May decrease the function of a vaccine when a bivalent or trivalent vaccine is used |
Range (1): it occurs between different species of virus, between the same species, and between inactivated and live viruses.
Mechanisms (3): (a) one virus blocks or destroys host-cell receptors, preventing the adsorption and penetration of the other; (b) the two viruses compete for replication materials — receptors, polymerase, translation initiation factors; (c) one virus induces the host cell to produce interferon, which prevents viral replication.
Application (2) — this is what “and its application” is asking for, and it is where marks are lost:
Advantages — interference stops viral replication and contributes to the patient's recovery; and an inactivated or live attenuated virus can be used as a vaccine, interfering with infection by the virulent virus.
Disadvantage — it may reduce the effectiveness of a bivalent or trivalent vaccine, since the components interfere with one another.
The deck's worked example is worth quoting: the poliovirus vaccine contains three types of poliovirus, which may interfere with one another, so they cannot be given simultaneously.
Most students can recite the three mechanisms and then lose the application marks. The application is the interesting half.
The oral polio vaccine contains three live attenuated poliovirus types. Give all three together and they compete for the same receptors, the same polymerase and the same translation machinery in the same gut cells — mechanisms (a) and (b) — so one type outgrows the others and the child is immunised against one type rather than three.
The same logic explains why live vaccines are given either on the same day or four weeks apart, never a few days apart: the interferon induced by the first (mechanism c) would blunt the second.
And it explains a piece of everyday clinical folklore with a real basis — that one viral infection can transiently protect against another. Interferon is not virus-specific; it is the host cell's general antiviral response, which is exactly why the previous unit's table lists viruses as interferon-sensitive and bacteria as interferon-resistant.
- Define viral interference. → When two viruses simultaneously infect one host cell, one may inhibit the replication of the other
- Between which viruses can it occur? → Between different species, between the same species, and between inactivated and live viruses
- Name the three mechanisms. → Blocking or destroying host-cell receptors to prevent adsorption and penetration · competition for replication materials (receptors, polymerase, translation initiation factors) · induction of interferon
- Name the advantages. → It stops viral replication and helps recovery; and inactivated or live attenuated virus can be used as a vaccine to interfere with the virulent virus
- Name the disadvantage. → It may reduce the effectiveness of a bivalent or trivalent vaccine — as with the three poliovirus types
Revision
Five definitions, eleven marks
| Term | Definition |
|---|---|
| ⭐ Defective virus | Genetically deficient; incapable of producing infectious progeny virions |
| Helper virus | Supplements the deficiency on co-infection, allowing progeny to be produced (AAV + adenovirus) |
| DIP | Defective interfering particle — occupies host-cell materials, interfering with normal replication |
| Non-permissive cell | A host cell that cannot provide the conditions for viral replication |
| Abortive infection | Infection producing no infectious progeny because the cell lacks the enzyme, energy or materials |
| ⭐ Viral interference | One virus inhibiting the replication of another in a simultaneously infected cell |
- Define defective virus for 4 marks. → A genetically deficient virus lacking genes for a complete infectious cycle, unable to produce infectious progeny; rescued by a helper virus (AAV with adenovirus, HDV with HBV), or acting as a DIP that interferes with normal replication
- Describe viral interference and its application for 7 marks. → Definition · range (different species, same species, inactivated with live) · three mechanisms (receptor blocking, competition for materials, interferon induction) · advantages (recovery; vaccines) · disadvantage (reduced effect of bivalent/trivalent vaccines)
- Which term applies when the CELL is at fault? → Abortive infection, in a non-permissive cell
- Which term applies when the VIRUS is at fault? → Defective virus