Respiratory Viruses
Influenza virus structure ★★★
Influenza viruses are enveloped viruses with a segmented −ssRNA genome. Every examinable property of this virus follows from those two words: enveloped and segmented.
| Part | Content |
|---|---|
| Core | −ssRNA, SEGMENTED — 8 segments for types A and B, 7 for type C · nucleoprotein (NP) · RNA polymerases PA, PB1, PB2 |
| Envelope — inner layer | M1 and M2 protein (M2 only on type A) · M1 is the matrix protein |
| Envelope — outer layer | Lipid bilayer derived from the host cell |
| Spikes | Haemagglutinin (HA) — pillar-like trimer · Neuraminidase (NA). Ratio approximately HA 5 : NA 1 |
| Antigen | Determines |
|---|---|
| NP and M1 protein | The TYPE — A, B or C |
| HA or NA protein | The SUBTYPE |
Surface glycoproteins HA and NA determine influenza virus antigenicity and host immunity. HA is the viral attachment protein, binding sialic acid (Unit 18 §5); NA cleaves sialic acid so progeny virus can be released.
- Describe the influenza genome. → Segmented negative-sense ssRNA — 8 segments in types A and B, 7 in type C
- Name the core proteins. → Nucleoprotein NP and RNA polymerases PA, PB1, PB2
- Name the envelope proteins. → Inner M1 and M2 (M2 only in type A); spikes HA and NA
- Which antigen determines type, and which subtype? → NP and M1 determine the type; HA or NA determine the subtype
- What do HA and NA do? → HA attaches to sialic acid; NA cleaves it to release progeny virus
The three types ★★★
| Type | Antigenic behaviour | Epidemiology | Hosts |
|---|---|---|---|
| Influenza A | Highly variable antigenically — drift AND shift | Causes most epidemics and ALL global pandemics | Also found in aquatic birds, ducks, domestic poultry, pigs and horses |
| Influenza B | Sometimes undergoes antigenic changes — drift only, never shift | Can cause epidemics | Humans |
| Influenza C | Antigenically STABLE | Sporadic mild illness | Humans |
Avian influenza A viruses — H5N1, H7N9 and H9N2 — cause sporadic human infections but have NOT acquired the ability for sustained human-to-human transmission.
- Compare the three influenza types. → A: highly variable, most epidemics and all pandemics, animal reservoirs. B: sometimes changes, epidemics only. C: antigenically stable
- Which animals carry influenza A? → Aquatic birds, ducks, domestic poultry, pigs, horses
- What limits H5N1 and H7N9? → They cause sporadic human infection but have not acquired sustained human-to-human transmission
⭐ Antigenic drift and antigenic shift ★★★
MINOR antigenic changes in HA and NA, occurring independently, caused by the ACCUMULATION OF POINT MUTATIONS.
A MAJOR antigenic change in HA or NA, resulting in a NEW INFLUENZA VIRUS SUBTYPE, caused by GENETIC REASSORTMENT of genome segments between human and animal viruses.
| Antigenic drift | Antigenic shift | |
|---|---|---|
| Magnitude | Minor | Major |
| Mechanism | Accumulation of point mutations — substitutions or deletions of amino acids in HA or NA | Genetic REASSORTMENT of genome segments between human and animal viruses |
| Result | A new strain within a subtype | A completely NEW SUBTYPE |
| Occurs in | Types A and B | Type A ONLY |
| Frequency | Constant and rapid; a new strain prevails 2–5 years | Less frequent, but with far more dramatic impact |
| Consequence | EPIDEMIC | PANDEMIC |
For the remaining marks:
Why it happens — it occurs only after a viral strain has become established in humans, and represents adaptation to the development of host antibodies. Each newly drifted strain prevails for 2–5 years before being replaced.
Its consequence — a strain unfamiliar to the population's antibody repertoire, and therefore a new EPIDEMIC; and the need for continual reformulation of influenza vaccines, which WHO and the CDC track.
Contrast it with antigenic SHIFT — a major change producing a new subtype, by genetic reassortment of genome segments between human and animal viruses, occurring in type A only and causing PANDEMICS. The examiner will expect the pair.
Go back to §1: eight separate segments. That single structural fact is the whole of antigenic shift.
If a pig — or a person — is infected simultaneously by a human influenza A virus and an avian one, both are dismantled into eight pieces inside the same cell. When progeny virions are assembled, the segments are shuffled between the two parents. A virus can emerge with the internal machinery of a human strain — so it grows well in humans — and an avian HA that no human immune system has ever seen.
Nobody has antibody. That is a pandemic. The 1957 and 1968 pandemics were both caused by genetic reassortment between human and avian influenza A virus.
Three consequences follow directly:
• Influenza B has never undergone shift — it has no animal reservoir to reassort with.
• The birds matter: certain species carry a reservoir of 15 influenza A subtypes, and swine act as the intermediate host in which mixing occurs.
• H5N1 and H7N9 are watched so closely precisely because they are avian subtypes already capable of infecting humans — one reassortment away from transmissibility.
Drift is a typing error; shift is swapping chapters between two books.
- Define antigenic drift. → Minor antigenic change in HA and NA from the accumulation of point mutations
- Define antigenic shift. → A major antigenic change in HA or NA producing a new subtype, caused by genetic reassortment of genome segments between human and animal viruses
- Which types show each? → Drift in A and B; shift in A only
- Which causes epidemics and which pandemics? → Drift → epidemics; shift → pandemics
- Why is shift possible at all? → The genome is segmented, so segments can be reassorted between co-infecting human and animal viruses
Immunity, vaccine and drugs ★★
- Because many different viruses cause respiratory infection, the diagnosis of influenza cannot reliably be made clinically and relies on laboratory assays
- Immunity to influenza is long-lived and SUBTYPE-SPECIFIC. Only antibodies to HA and NA are protective
- Both inactivated and live-virus vaccines exist, but are continually rendered obsolete as new antigenic variants arise
- Antiviral drugs exist, but resistant viruses emerge frequently — especially to the M2 ion channel inhibitors
The two drug classes from Unit 21 §5 map onto this virus exactly: amantadine and rimantadine are the M2 ion channel inhibitors, blocking uncoating; zanamivir and oseltamivir are neuraminidase inhibitors, blocking release.
- Why can influenza not be diagnosed clinically? → Many different viruses cause similar respiratory infections; laboratory assays are needed
- What kind of immunity does influenza confer? → Long-lived and subtype-specific; only anti-HA and anti-NA antibodies are protective
- Why must the vaccine be reformulated? → New antigenic variants arise continually through drift
- Which drugs, and which resist? → M2 ion channel inhibitors (amantadine, rimantadine) — resistance is frequent; and neuraminidase inhibitors (zanamivir, oseltamivir)
The paramyxoviruses ★★★
A large family; six genera contain human pathogens: parainfluenza viruses, respiratory syncytial virus and human metapneumovirus (respiratory disease); measles virus, mumps virus, and Hendra and Nipah viruses (zoonotic encephalitides).
⭐ Common properties — contrast every line with influenza
- Enveloped RNA viruses with a negative-sense, NON-SEGMENTED genome
- ALL are antigenically STABLE
- Transmitted by contact or large droplets; initiate infection through the respiratory tract
- The entire replication cycle occurs in the CYTOPLASM
| Virus | Disease |
|---|---|
| Respiratory syncytial virus (RSV) | The most important cause of lower respiratory tract illness in infants and young children. Serious bronchiolitis or pneumonia occurs most often in infants aged 6 WEEKS TO 6 MONTHS. Elderly adults are also susceptible. Ribavirin is approved for treatment in infants |
| Human metapneumovirus | Young children, the immunocompromised and elderly adults; disease resembles RSV |
| Parainfluenza viruses | Respiratory illness at all ages; most serious in infants and young children |
| Mumps virus | A SYSTEMIC disease, with about HALF of infections causing swelling of the salivary glands. Many infections are asymptomatic |
| Measles virus (rubeola) | A highly infectious, disseminated infection characterised by a RASH. Serious complications including pneumonia and encephalitis can occur. INAPPARENT INFECTIONS ARE RARE |
| Hendra and Nipah viruses | Animal paramyxoviruses able to infect humans; they cause encephalitis with a high mortality rate. There is no treatment |
There are single serotypes of measles virus and mumps virus, and infection confers LIFELONG immunity. No vaccines are available for parainfluenza viruses, RSV or human metapneumovirus; effective vaccines exist for both measles and mumps. Detection of viral RNA or viral antigen is the preferred method of diagnosis, and reinfections are common with the respiratory viruses.
Put the two families side by side and one property explains the whole difference in public health.
Influenza: segmented genome, highly variable, drift and shift. Immunity is subtype-specific and the virus outruns it. The vaccine must be reformulated every year, and reinfection is normal.
Paramyxoviruses: non-segmented genome, antigenically stable, single serotype. No segments means no reassortment, so no shift is even possible. Infection with measles or mumps confers lifelong immunity, and a vaccine made decades ago still works — which is why measles is theoretically eradicable and influenza is not.
One caution against over-applying it: RSV and parainfluenza are also stable, yet reinfection is common and there is no vaccine. Their problem is different — the immunity they induce is poor and short-lived, especially at the mucosa, not that the virus changes. And measles makes the point in reverse: inapparent infections are rare, so essentially everyone infected is recognisably ill — which is exactly what makes elimination programmes measurable.
- Give the four common properties of paramyxoviruses. → Enveloped, negative-sense NON-segmented RNA · all antigenically stable · transmitted by contact or large droplets via the respiratory tract · entire replication cycle in the cytoplasm
- Which is the most important cause of lower respiratory illness in infants, and at what age? → RSV; bronchiolitis or pneumonia most often at 6 weeks to 6 months
- What treats RSV in infants? → Ribavirin
- Describe mumps and measles. → Mumps: systemic, about half with salivary gland swelling, many asymptomatic. Measles: highly infectious disseminated infection with rash; pneumonia and encephalitis as complications; inapparent infection rare
- Which have vaccines? → Measles and mumps; not parainfluenza, RSV or human metapneumovirus
- What do Hendra and Nipah cause? → Encephalitis with high mortality, with no treatment
Rubella and the coronaviruses ★★★
| Rubella (German measles) | Detail |
|---|---|
| Classification | Classified as a TOGAVIRUS, but transmitted by respiratory secretions rather than arthropods |
| Disease | The MILDEST of the common viral exanthems |
| The danger | Infection during EARLY PREGNANCY can result in serious harm to the fetus, including fetal death. Children born with congenital rubella may have a variety of physical problems and developmental abnormalities |
| Prevention | A rubella vaccine is available. Congenital rubella can be prevented by childhood vaccination, so that women of childbearing age are immune |
| Coronaviruses | Detail |
|---|---|
| Structure | Enveloped, with a genome of single-stranded POSITIVE-sense RNA that is the LARGEST genome among RNA viruses |
| Usual disease | Human coronaviruses typically cause common colds |
| SARS | A novel coronavirus that originated in a non-human host caused a worldwide outbreak of SARS in 2003 |
| MERS-CoV | First detected in 2012; can cause severe respiratory disease in some patients |
| Distribution | Human coronaviruses are distributed worldwide, with the exception of the SARS and MERS viruses |
| Treatment | There is no proven treatment and no vaccine |
Both halves of that sentence are on the slide, and the contradiction is the point.
In a child, rubella is trivial — a low fever and a fleeting rash, milder than measles, milder than chickenpox. In the first trimester it is a catastrophe, because the virus crosses the placenta while organs are forming.
This is Unit 20 §2's vertical transmission with malformation — rubella heading the list alongside CMV and HSV. Congenital rubella syndrome classically gives cataracts, deafness and cardiac defects.
And the prevention strategy is subtle: you do not vaccinate to protect the child, who needs little protection. You vaccinate children so that women reach childbearing age already immune. The vaccine's target and its beneficiary are different people, a generation apart.
Note also the timing rule that follows from Unit 21 §5: rubella vaccine is live, so it is contraindicated during pregnancy — the one time the disease matters most. Immunity must be in place beforehand.
- How is rubella classified and transmitted? → As a togavirus, but transmitted by respiratory secretions rather than arthropods
- Why does rubella matter? → It is the mildest common exanthem, but infection in early pregnancy causes fetal death or congenital rubella with physical and developmental abnormalities
- How is congenital rubella prevented? → By childhood vaccination, so that women of childbearing age are already immune
- Describe the coronavirus genome. → Enveloped, single-stranded positive-sense RNA — the largest genome among RNA viruses
- What do coronaviruses cause? → Usually common colds; SARS in 2003 from a novel coronavirus of non-human origin; MERS-CoV from 2012. No proven treatment or vaccine
Revision
The whole unit on one screen
| Question | Answer |
|---|---|
| Influenza genome? | Segmented −ssRNA — 8 (A, B), 7 (C) |
| Type vs subtype antigens? | NP and M1 vs HA or NA |
| ⭐ Antigenic drift? | Minor change in HA/NA by point mutations → new strain → epidemic; types A and B |
| ⭐ Antigenic shift? | Major change by reassortment of segments with animal virus → new subtype → pandemic; type A only |
| Protective antibody? | Only to HA and NA; subtype-specific |
| Paramyxovirus genome? | Non-segmented −sense RNA; antigenically stable; replicates in cytoplasm |
| RSV? | Commonest LRT illness in infants; bronchiolitis at 6 wk–6 mo; ribavirin |
| Measles? | Highly infectious rash illness; pneumonia and encephalitis; inapparent infection rare; SSPE as late complication |
| Mumps? | Systemic; half get salivary gland swelling; many asymptomatic |
| Rubella? | Togavirus by respiratory spread; mildest exanthem but teratogenic in early pregnancy |
| Coronavirus? | Enveloped +ssRNA, largest RNA genome; colds, SARS 2003, MERS 2012; no vaccine or proven treatment |
- Define antigenic drift for 4 marks. → A minor antigenic change in influenza HA or NA caused by accumulated point mutations, representing adaptation to host antibody; each strain prevails 2–5 years, causes epidemics, and forces annual vaccine reformulation
- Contrast drift with shift. → Drift: minor, point mutations, types A and B, epidemics. Shift: major, reassortment of genome segments with animal viruses, type A only, new subtype, pandemics
- Why can influenza B not undergo shift? → It has no animal reservoir to reassort with
- Give four properties of paramyxoviruses. → Enveloped, non-segmented negative-sense RNA · antigenically stable · contact or large-droplet spread via the respiratory tract · replication entirely in the cytoplasm
- Why is rubella vaccination given to children? → So that women reach childbearing age immune, preventing congenital rubella — the vaccine is live and cannot be given in pregnancy