General Virology · Unit 20 of 28
Viral Infection and Immunity
01
The characteristics of viral infection ★★
Viral infection
The process of a virus entering and multiplying in the human body.
| Characteristic | Example |
|---|---|
| a. A particular disease may be caused by several viruses | Viral hepatitis — HAV, HBV, HCV, HDV, HEV. The common cold — many respiratory tract viruses |
| b. A particular virus may cause several different diseases, or no observable symptoms | HSV-1 → gingivostomatitis, pharyngitis, herpes labialis (cold sores), genital herpes, encephalitis, or keratoconjunctivitis |
Test yourself
- Define viral infection. → The process of a virus entering and multiplying in the human body
- Give the two characteristics with examples. → One disease from several viruses (viral hepatitis from HAV–HEV; the common cold); one virus causing several diseases or none (HSV-1)
02
⭐ Modes and routes of transmission ★★★
Horizontal transmission
Direct host-to-host transmission of viruses.
Vertical transmission — the 2019 Section I term
Viral transmission from one generation to the next, or from parent to the young, via the PLACENTA, the BIRTH CANAL and BREASTFEEDING.
Routes — the portal of entry
| Horizontal route | Detail |
|---|---|
| Respiratory tract | The MOST COMMON portal of entry — droplets, aerosols, nasal secretions or saliva |
| GI tract (faecal–oral route) | The SECOND most common route — naked viruses |
| Skin or mucosa | Skin abrasion — papilloma virus · insect stings — encephalitis B virus, dengue virus · animal bite — rabies virus |
| Urogenital tract | Direct or indirect contact |
| Other routes | Blood transfusion, injection, organ transplantation |
| Vertical route — placenta, birth canal, breastfeeding | Viruses |
|---|---|
| Congenital MALFORMATION | Rubella virus · cytomegalovirus (CMV) · HSV |
| Congenital infection WITHOUT malformation | HBV · HIV |
⭐ The 2019 Section I term
“Vertical transmission” — 4 marks, 2019 Section I
Transmission of a virus from one generation to the next — from parent to offspring — via the placenta, the birth canal, or breastfeeding.
For the remaining marks, contrast it and give examples:
Contrast with horizontal transmission, which is direct host-to-host spread.
Two groups of examples — this is the discriminating detail:
• Congenital MALFORMATION: rubella virus, CMV, HSV
• Congenital infection WITHOUT malformation: HBV, HIV
You may add the bacterial example from Unit 17 — Treponema pallidum crossing the placenta to cause congenital syphilis — and the point that vertical transmission is why antenatal screening for HBV, HIV, syphilis and rubella immunity exists.
⚠️ Do not confuse this with the bacterial-genetics sense of vertical gene transfer (Unit 4 §4), which means passing genes to daughter cells at division. The 2019 paper sets the virological meaning.
For the remaining marks, contrast it and give examples:
Contrast with horizontal transmission, which is direct host-to-host spread.
Two groups of examples — this is the discriminating detail:
• Congenital MALFORMATION: rubella virus, CMV, HSV
• Congenital infection WITHOUT malformation: HBV, HIV
You may add the bacterial example from Unit 17 — Treponema pallidum crossing the placenta to cause congenital syphilis — and the point that vertical transmission is why antenatal screening for HBV, HIV, syphilis and rubella immunity exists.
⚠️ Do not confuse this with the bacterial-genetics sense of vertical gene transfer (Unit 4 §4), which means passing genes to daughter cells at division. The 2019 paper sets the virological meaning.
2019 Microbiology paper, Section I · TMU Microbiology Chapter 23 — Viral Infection and Immunity
Test yourself
- Define horizontal and vertical transmission. → Horizontal: direct host-to-host spread. Vertical: from one generation to the next, via placenta, birth canal or breastfeeding
- Name the routes of horizontal transmission in order of frequency. → Respiratory tract (most common) · GI/faecal–oral (second, naked viruses) · skin or mucosa (abrasion, insect sting, animal bite) · urogenital · blood transfusion, injection, transplantation
- Which vertically transmitted viruses cause malformation, and which do not? → Malformation: rubella, CMV, HSV. Without malformation: HBV, HIV
- Why are faecal–oral viruses naked? → They have no fragile lipid envelope to be destroyed by bile and digestive conditions
03
Viral spread in the host ★★
| Type | Detail |
|---|---|
| Localised infection | The infection remains at the site of primary infection — influenza virus → upper respiratory tract infection; HRV → GI tract infection |
| Systemic infection — via blood or lymph | Measles, poliovirus — VIRAEMIA |
| Systemic infection — via nerves | HSV, VZV, rabies virus. Transport is often intra-axonal, and virions may become latent in nerve cell bodies (HSV, VZV) |
Test yourself
- Localised vs systemic infection? → Localised stays at the primary site (influenza in the URT); systemic disseminates via blood or lymph (measles, poliovirus — viraemia) or via nerves (HSV, VZV, rabies)
- How do neurotropic viruses travel? → Intra-axonally; HSV and VZV may then remain latent in nerve cell bodies
04
⭐ Types of viral infection ★★★
Inapparent (subclinical) infection
The virus multiplies in host cells without causing clinical symptoms. Significance: it is a source of infection · it is misdiagnosed or not diagnosed · the host acquires immunity.
Apparent infection
Viruses multiply in host cells and cause clinical symptoms.
| Apparent infection | Detail |
|---|---|
| Acute infection | Short incubation, sudden onset, short duration — several days to weeks. Common cold, influenza, hepatitis A and E |
| Persistent infection | Viruses persist in the host for a long period, sometimes for the whole life. Four forms — below |
⭐ The four forms of persistent infection
| Form | Definition | Example |
|---|---|---|
| 1 · Chronic infection ⭐ | After acute infection the viruses are NOT eliminated, and there is intermittent multiplication and shedding of viruses. Virus can be continuously detected, often at a low level. Mild or no clinical symptoms may be present | Hepatitis B |
| 2 · Latent infection | Viruses persist in the host in a HIDING form and there is NO production of infectious viruses. Under some conditions the latent viruses are activated and multiply to produce clinical symptoms | HSV-1 — latent in the trigeminal ganglia, recurring as cold sores · HSV-2 — sacral ganglia · VZV — spinal dorsal root ganglia and cranial sensory ganglia, recurring as zoster |
| 3 · Slow virus infection (delayed infection) | A long incubation lasting months or years, with no clinical symptoms although infectious viruses may multiply; then chronic and progressive disease appears and eventually develops into fatal infection | HIV → AIDS · Prion → kuru, CJD |
| 4 · Acute infection with rare late complication | An acute illness resolves, and a fatal complication appears years later | Measles virus → SSPE (subacute sclerosing panencephalitis) — progressive degeneration of brain function; spasm, coma and death |
⭐ The 2020 Section I term
“Chronic virus infections” — 4 marks, 2020 Section I
A form of PERSISTENT infection in which, after the acute infection, the viruses are not eliminated from the host; there is intermittent multiplication and shedding of virus, the virus can be continuously detected (often at a low level), and mild or no clinical symptoms may be present.
Three things secure the remaining marks:
Place it in the classification — it is one of the four forms of persistent infection, alongside latent infection, slow virus infection and acute infection with rare late complication.
Distinguish it from latent infection, which is the trap: in a chronic infection virus is continuously demonstrable and is being shed; in a latent infection the virus is hidden and no infectious virus is produced until reactivation.
Give the example — hepatitis B (and hepatitis C). The clinical importance is that the patient is a continuing source of infection while feeling well, and is at risk of cirrhosis and hepatocellular carcinoma.
Three things secure the remaining marks:
Place it in the classification — it is one of the four forms of persistent infection, alongside latent infection, slow virus infection and acute infection with rare late complication.
Distinguish it from latent infection, which is the trap: in a chronic infection virus is continuously demonstrable and is being shed; in a latent infection the virus is hidden and no infectious virus is produced until reactivation.
Give the example — hepatitis B (and hepatitis C). The clinical importance is that the patient is a continuing source of infection while feeling well, and is at risk of cirrhosis and hepatocellular carcinoma.
2020 Microbiology paper, Section I · TMU Microbiology Chapter 23 — Viral Infection and Immunity
Mechanisms of persistent infection
- No or weak antigenicity of the virus — e.g. prion
- Mutation of viral antigens
- Viral genes integrate into the cellular chromosome — e.g. EBV, HIV
- Viruses destroy immune cells — e.g. HIV destroys CD4⁺ T cells
- Host immunity decreases — from immunosuppressive agents such as steroids · some infections such as tuberculosis · tumour or chronic disease such as diabetes
Chronic, latent, slow — three words students swap constantly
Ask one question of each: is infectious virus being produced right now?
Chronic — yes, continuously, at a low level, with shedding. The patient is infectious and often symptom-free. Hepatitis B.
Latent — no, none at all. The genome is hiding in a nerve ganglion producing nothing, until a trigger reactivates it. Between attacks the patient is not infectious; during a cold sore or a shingles rash, very much so. HSV, VZV.
Slow — yes, but silently for years, and the disease when it comes is progressive and fatal. HIV, prions.
Acute with late complication is the odd one: the acute illness resolved completely and the complication arrives years later. Measles and SSPE.
One question — is virus being made? — sorts all four.
Test yourself
- Define inapparent infection and give its significance. → The virus multiplies without causing symptoms; it is a source of infection, is misdiagnosed or missed, and confers immunity
- Define acute and persistent infection. → Acute: short incubation, sudden onset, days to weeks. Persistent: the virus stays in the host a long time, sometimes for life
- Name the four forms of persistent infection. → Chronic · latent · slow virus (delayed) · acute infection with rare late complication
- Chronic vs latent? → Chronic: virus continuously detectable and shed intermittently, mild or no symptoms (HBV). Latent: virus hidden with NO infectious virus produced until reactivation (HSV, VZV)
- Give an example of slow virus infection and of late complication. → HIV → AIDS and prions → kuru/CJD; measles → SSPE
- Name five mechanisms of persistence. → Weak or absent antigenicity · antigenic mutation · integration into the host chromosome · destruction of immune cells · decreased host immunity
05
⭐ Viral pathogenesis ★★★
“Please describe the pathogenesis of viruses” is 2019 Section III, 7 marks, and the TMU homework list phrases it more fully: “Please describe the types, routes of viral infection and the mechanism of viral pathogenesis.” The deck divides pathogenesis in two.
| Meaning | |
|---|---|
| A · Cytopathogenesis | Viral replication directly damages the host cell — DIRECT injury via viral replication |
| B · Immunopathogenesis | Virus-induced immunopathologic injury — INDIRECT injury via the host immune response against the viral infection |
A · Direct damage — four mechanisms
| Mechanism | Detail |
|---|---|
| a · Host cell lysis (cytolytic / cytocidal infection) | Naked viruses — e.g. poliovirus, adenovirus. Mechanism: blocks synthesis of cellular macromolecules · produces toxic proteins · destroys organelles — e.g. increased lysosome permeability → cell autolysis |
| b · Steady-state infection | Viral budding release · alteration of the host cell membrane · new antigens appear on the host cell membrane (viral antigens and cellular autoantigens such as LSP) · syncytia formation |
| c · Integration | Viral DNA integrates into the cellular chromosome → cell transformation (normal cell → immortalised cell) → TUMOUR; and escape from immune clearance |
| d · Apoptosis | Induces host cell apoptosis — programmed cell death |
Two definitions from this section
CPE (cytopathic effect)
Morphological changes of cells due to viral infection, which can be observed under the light microscope — e.g. rounding, necrosis, cell lysis, cell detachment from the flask wall, inclusion body formation, giant cell formation, cytoplasmic vacuolisation.
Inclusion body
Round or oval, acidophilic or basophilic structures in the cytoplasm or nucleus, or both, which can be observed under the light microscope.
Negri body — a 2020 Section I term
Round or oval, EOSINOPHILIC INTRACYTOPLASMIC inclusion bodies, observed under the light microscope within some NERVE CELL cytoplasm infected with RABIES VIRUS. See the Rabies unit.
B · Immunopathogenesis
| Mechanism | Detail |
|---|---|
| Humoral immunopathologic injury | New antigens → antigen–antibody complexes activate complement. Circulating antigen–antibody complexes deposit in blood vessels, kidney, joints and brain → vasculitis · glomerulonephritis (with albuminuria and haematuria) · arthritis · mental confusion |
| Cell-mediated immunopathologic injury | Induces a CTL cytotoxic effect. Viral proteins share common antigens with host cell proteins → autoimmune response |
| Virus-induced immunosuppression | HIV, measles virus, rubella virus |
⭐ The 2019 Section III brief answer
“Please describe the pathogenesis of viruses.” (7 marks, 2019 Section III)
Structure the answer in the deck's two halves — that division alone is worth a mark.
A · Cytopathogenesis — direct injury by viral replication (4):
(a) Host cell lysis — cytolytic/cytocidal infection by naked viruses such as poliovirus and adenovirus, by blocking synthesis of cellular macromolecules, producing toxic proteins and destroying organelles.
(b) Steady-state infection — budding release, alteration of the host cell membrane, new antigens on the membrane, syncytia formation.
(c) Integration — viral DNA integrates into the cellular chromosome, causing cell transformation and tumour, and allowing escape from immune clearance.
(d) Apoptosis — induction of programmed cell death.
B · Immunopathogenesis — indirect injury by the host response (3):
Humoral — antigen–antibody complexes activate complement and deposit in vessels, kidney, joints and brain, giving vasculitis, glomerulonephritis, arthritis and mental confusion.
Cell-mediated — CTL cytotoxicity, and autoimmunity where viral proteins share antigens with host proteins.
Immunosuppression — HIV, measles, rubella.
If the question is the fuller homework version, add the types of infection (§4) and the routes (§2) first.
A · Cytopathogenesis — direct injury by viral replication (4):
(a) Host cell lysis — cytolytic/cytocidal infection by naked viruses such as poliovirus and adenovirus, by blocking synthesis of cellular macromolecules, producing toxic proteins and destroying organelles.
(b) Steady-state infection — budding release, alteration of the host cell membrane, new antigens on the membrane, syncytia formation.
(c) Integration — viral DNA integrates into the cellular chromosome, causing cell transformation and tumour, and allowing escape from immune clearance.
(d) Apoptosis — induction of programmed cell death.
B · Immunopathogenesis — indirect injury by the host response (3):
Humoral — antigen–antibody complexes activate complement and deposit in vessels, kidney, joints and brain, giving vasculitis, glomerulonephritis, arthritis and mental confusion.
Cell-mediated — CTL cytotoxicity, and autoimmunity where viral proteins share antigens with host proteins.
Immunosuppression — HIV, measles, rubella.
If the question is the fuller homework version, add the types of infection (§4) and the routes (§2) first.
2019 Microbiology paper, Section III · TMU homework list · TMU Microbiology Chapter 23 — Viral Infection and Immunity
Test yourself
- Name the two divisions of viral pathogenesis. → Cytopathogenesis (direct damage by replication) and immunopathogenesis (indirect damage by the host immune response)
- Name the four direct mechanisms. → Host cell lysis · steady-state infection · integration → transformation and tumour · apoptosis
- Define CPE. → Morphological changes of cells due to viral infection, visible by light microscopy — rounding, necrosis, lysis, detachment, inclusion bodies, giant cells, vacuolisation
- Define an inclusion body and a Negri body. → Round or oval acidophilic or basophilic structures in cytoplasm or nucleus; Negri bodies are eosinophilic intracytoplasmic inclusions in nerve cells infected with rabies virus
- Name the three immunopathologic mechanisms. → Humoral (immune-complex deposition causing vasculitis, glomerulonephritis, arthritis, mental confusion) · cell-mediated (CTL cytotoxicity and autoimmunity) · virus-induced immunosuppression
06
Anti-viral immunity and interferon ★★★
| Non-specific immunity | Detail |
|---|---|
| NK cells | Limit the spread of infection at the early stage |
| Interferon (IFN) | The FIRST LINE of defence against viral infection |
Interferon (IFN)
Host-encoded proteins which can inhibit viral replication, produced by humans, animals or cultured cells in response to viral infection or other inducers.
Bioactivity of IFNs: antiviral effects · immunomodulatory effects · antitumour effects.
Induction and mechanism of action
- Viral infection or IFN inducers activate the IFN genes
- The IFN genes are transcribed and translated into IFNs
- IFNs bind to receptors on NEIGHBOURING cells and activate cellular genes to produce ANTIVIRAL PROTEINS (AVP), which inhibit viral protein synthesis
⭐ Characteristics of IFN action
- INDIRECT inhibition of viral replication
- BROAD-SPECTRUM antiviral activity — NOT virus-specific
- HOST SPECIES-specific
| Specific immunity | Detail |
|---|---|
| Humoral | Antibody response — neutralising antibody (IgG, IgM and IgA) |
| Cellular | CTL, activated macrophages, and soluble factors (lymphokines and monokines) |
Three characteristics, three consequences
Those three lines are dense, and each has a practical meaning.
Indirect. Interferon does not touch the virus. It binds a receptor on the neighbouring cell and makes that cell manufacture antiviral proteins. So the infected cell is already lost; interferon protects the cells around it. That is why it acts fastest as a containment mechanism — the first line of defence, ahead of antibody, which takes days.
Broad-spectrum, not virus-specific. One interferon response works against any virus, which is the opposite of antibody. It is also why interference (Unit 19 §4, mechanism c) works between unrelated viruses, and why the previous unit's table lists all viruses as interferon-sensitive.
Host species-specific. Human interferon works in human cells and not in mouse cells. Practically: interferon used as a drug — for hepatitis B and C — must be human interferon, which is why it was scarce and expensive until recombinant production. You cannot raise it in animals as you can antitoxin.
Test yourself
- Define interferon. → Host-encoded proteins that inhibit viral replication, produced by humans, animals or cultured cells in response to viral infection or other inducers
- Name its three bioactivities. → Antiviral, immunomodulatory, antitumour
- Describe its induction and action. → Viral infection activates IFN genes → IFN is synthesised and released → binds receptors on neighbouring cells → activates genes producing antiviral proteins (AVP) that inhibit viral protein synthesis
- Name the three characteristics of IFN action. → Indirect · broad-spectrum and not virus-specific · host species-specific
- Name the specific anti-viral immune mechanisms. → Humoral — neutralising IgG, IgM, IgA; cellular — CTL, activated macrophages, lymphokines and monokines
07
Revision
⭐ The three exam items owned by this unit
| Paper | Item | Section here |
|---|---|---|
| 2019 Section I | Vertical transmission (4 marks) | §2 |
| 2020 Section I | Chronic virus infections (4 marks) | §4 |
| 2019 Section III | Pathogenesis of viruses (7 marks) | §5 |
The whole unit on one screen
| Question | Answer |
|---|---|
| Commonest route? | Respiratory tract; then faecal–oral (naked viruses) |
| ⭐ Vertical transmission? | Parent to offspring via placenta, birth canal, breastfeeding |
| Malformation vs not? | Rubella, CMV, HSV vs HBV, HIV |
| Spread in host? | Localised · systemic via blood/lymph (viraemia) · systemic via nerves |
| Types? | Inapparent vs apparent (acute or persistent) |
| 4 persistent forms? | Chronic · latent · slow virus · acute with late complication |
| ⭐ Chronic? | Virus not eliminated, intermittent shedding, continuously detectable, mild or no symptoms — HBV |
| Latent? | No infectious virus produced until reactivation — HSV, VZV |
| ⭐ Pathogenesis? | Cytopathogenesis (lysis, steady state, integration, apoptosis) + immunopathogenesis (humoral, cell-mediated, immunosuppression) |
| CPE? | Morphological cell changes visible by light microscopy |
| Negri body? | Eosinophilic intracytoplasmic inclusion in rabies-infected nerve cells |
| IFN action? | Indirect · broad-spectrum · species-specific; makes neighbouring cells produce AVP |
Test yourself — the whole unit
- Define vertical transmission for 4 marks. → Transmission from one generation to the next via placenta, birth canal or breastfeeding; contrasted with horizontal host-to-host spread; rubella, CMV and HSV cause malformation, HBV and HIV congenital infection without it
- Define chronic virus infection for 4 marks. → A form of persistent infection in which virus is not eliminated after the acute illness, multiplies and is shed intermittently, is continuously detectable at low level, with mild or no symptoms — e.g. HBV; distinct from latent infection, in which no infectious virus is produced
- Describe the pathogenesis of viruses for 7 marks. → Direct cytopathogenesis (cell lysis, steady-state infection, integration causing transformation and tumour, apoptosis) and indirect immunopathogenesis (immune-complex humoral injury, CTL and autoimmune cell-mediated injury, virus-induced immunosuppression)
- Give the three characteristics of interferon action. → Indirect inhibition, broad-spectrum and not virus-specific, host species-specific
- Name the four forms of persistent infection with examples. → Chronic (HBV) · latent (HSV, VZV) · slow virus (HIV, prions) · acute with rare late complication (measles → SSPE)