Neuraminidase in Viral Pathogenicity

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Neuraminidase in Viral Pathogenicity

Neuraminidase in Viral Pathogenicity

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Influenza

Part 1

Aims of the lecture

To provide an introduction to the influenza virus and how it causes disease in humans.

Learning outcomes

• Describe the basic structure of the influenza virus

• Explain how the virus infects and replicates • Explain the importance of Haemagglutinin and Neuraminidase in viral pathogenicity

• Compare and contrast the different diagnostic techniques used to identify flu

What is influenza? • An infectious disease commonly called flu • Caused by a family of influenza viruses; A, B and C • Can infect birds and mammals including humans • Symptoms of the disease include chills, fever, runny nose, sore throat, muscle pains, fatigue, and headache

• Spread in humans by direct contact with infected individual or contaminated object and by inhalation of virus particles

• Distinct from the “common” cold, parainfluenza and stomach flu. Also different from haemophilus influenzae which is a bacterial form of respiratory disease

Influenza virus • Negative sense single stranded RNA virus – i.e cannot be directly translated to protein, must first be transcribed to sense RNA

• Influenza virus A, B and C distinguished by the nucleoprotein and the matrix protein

• All infect humans and – A infects other mammals and birds (pandemic) – B infects seals – C infects pigs and dogs

• Influenza C tends to cause mild disease

Influenza A

Influenza proteins (and nucleic acids)

Protein/Nucleic acid Function

Neuraminidase (NA) Membrane glycoprotein, cleaves sialic acid groups from host glycoproteins. Required for release from host cell

Haemagglutinin (HA) Membrane glycoprotein, major viral antigen. Required for entry and release from host cell

Matrix protein (M1) Provides strength and rigidity

M2 Ion channel required for pH maintenance

B1, PB2, PA RNA polymerases required for transcription of viral RNA

8 RNA segments Code 12 viral proteins

Influenza A • Generally thought to be the most pathogenic • Causes epidemics and pandemics (4 in the last 100 years)

• Classified according to their HA and NA subtypes – H1 – H18 (H18 found in 2013 in a Peruvian bat) – N1 – N10

• All subtypes can infect birds except H17N10 found only in bats

• Only H1N1 and H3N2 currently in circulation among humans

Antigenic variation

• Poor proof reading rates in viral polymerases leads to point mutation in viral HA (genetic drift)

• Occasionally mutated HA has an advantage and new HA strains emerge and infect

• Reassortment of HA in animals infected with more than one strain of influenza A also lead to new HA often novel to the human host

Influenza virus

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