Assignment: Haemagglutination in RBC

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Assignment: Haemagglutination in RBC

Assignment: Haemagglutination in RBC

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Haemagglutinin • HA named because it causes haemagglutination in RBC

• Binds to sialic acid on epithelial cells to initiated viral entry

• Sialic acid is linked to galactose in different configurations

a2-3 linkage

Haemagglutinin linkages

• Isolates from different species vary in ability to bind to sialic acid/galactose – Human and swine isolates prefer Sia-Gal in an α2- 6 linkage

– Avian and equine isolates prefer α2-3 linkage

Haemagglutinin linkages • Isolates from different species vary in ability to bind to sialic acid/galactose – Human and swine isolates prefer Sia-Gal in an α2-6 linkage

– Avian and equine isolates prefer α2-3 linkage • Human epithelial cells (main target for flu) have the α2-6 configuration whereas goblet cells lower in the respiratory tract have α2-3

• Swine respiratory tract has both binding sites (and possibly more variation)

• Pigs act as mixing bowl

Neuraminidase

• HA binds to sialic acid on cell so prevents release of new virion after budding

• NA cleaves sialic acid from sugar allowing virion to be released

• Cleavage is not equivalent by all subtypes • Most strains have a preference for the α2-3 configuration

Viral replication

1. Virion is endocytosed

2. RNA released into the cytosol and then enter the nucleus 3b. Transcription occurs

6. NEP and M1 traffic newly replicated RNA to the membrane

3a-4. Transcribed RNA is transported to cytoplasm for translation or remains in nucleus

5. New viral proteins are synthesised. 5a. Other proteins returned to nucleus to form new vRNA particles 5b. NA and HA transported to membrane.

7. New virions bud off

Influenza • Occurs seasonally–generally between October and April in

the UK • Symptoms include:

– High temperature – Aches and pains in joints – Headaches – Watery eyes – Fatigue – Sore throat and watery discharge from nose – Diarrhoea

• At risk groups given flu vaccine seasonally • Nasal spray vaccine for 2, 3 and 4 year olds introduced in

September 2014

Why is flu seasonal? • People are indoors leading to increase in transmission • Less ultraviolet radiation may reduce the likelihood of the virus being

damaged or killed • Cold temperatures lead to drier air, which may dehydrate mucus

membranes • Aerosol transmission of the virus is enhanced when the air is cold and

dry – Virus degraded in moist air – Infected hosts shedding the virus for a longer period of time in cold

• The virus may linger longer on exposed surfaces (doorknobs, countertops, etc.) in colder temperatures

• Influenza virus has a “butter-like coating”. The coating melts when it enters the respiratory tract – Cold – coating becomes a hardened shell – Warm – coating melts before the virus reaches the respiratory tract

Transmission of flu • Inhaling infected droplets when people sneeze, cough or speak – Indirect – Up to 1 metre

• Inhaling droplets through direct contact – Kissing

• Indirect transmission (fomite transmission) – e.g. hand to mucous

Diagnosing flu

H1N1 09

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