Final- Orthomyxoviridae

Question 1

Taxonomy of Orthomyxoviridae

Answer 1

Family: Orthomyxoviridae

Genus: Influenza A, Influenza B, Influenza C, Thogotovirus and Isavirus

Influenza A genus contains Human, equine, swine and domestic

poultry viruses

Influenza B genus contains human viruses

Influenza C genus contains human and swine viruses that rarely cause disease

• Thogotovirus genus contains tick borne viruses which infect livestock and humans in Africa, Europe and Asia – not well studied
• Isavirus genus has only one member, infectious salmon anemia virus
• Orthomyxoviruses cause diseases referred to as “influenza” hence generally called influenza viruses

Question 2

Current classification of orthomyxoviruses

Answer 2

• Based on the type of hemagglutinin and neuraminidase
• There are 16 hemagglutinin (H) and 9 Neuraminidase (N) types

Question 3

Naming of influenza viruses

Answer 3

• Type A, B, C
• Host (swine, horse, chicken, turkey etc.)
• geographical origin
• Strain number
• Year of isolation
• Hemagglutinin and neuraminidase subtype

The host of origin is not specified for influenza viruses isolated from humans

Examples:

A/equine/Miami/1/1963 (H3N8) – prototype influenza virus

A/swine/Iowa/15/1930 (H1N1) – prototype swine influenza virus

A/Hongkong/1/1968 (H3N2) – the virus that caused the human pandemic in 1968

A/chicken/Scotland/1959 (H5N1) – the first high pathogenicity avian influenza virus of the H5 subtype

Question 4

Virion morphology

Answer 4

• Orthomyxoviruses are pleomorphic, often spherical, sometimes filamentous

• 80-120 nm at their smallest dimension
• Lipid layer with large spikes surrounding 6 or 8 s helically symmetrical

nucleocapsid segments of different sizes

• Genome is segmented

Question 5

Two types of glyocoprotein spikes for influenza A and B

Answer 5

Two types of glyocoprotein spikes for influenza A and B - homotrimer HA and homotetramer NA

Question 6

Influenza C lack

Answer 6

Influenza C lack neuraminidase and have only 1 type of glycoprotein spikes – the hemagglitinin is multifunctional – esterase molecule

Question 7

Isavirus also has

Answer 7

Isavirus also has hemagglutinin esterase and F protein

Question 8

Regardless of the glycoprotein structure, the HA performs 3 functions:

Answer 8

• receptor binding
• receptor cleavage
• membrane fusion

Question 9

Structure of the Influenza A viruses

Answer 9

• Lipid envelope derived from the host cell
• Envelope harbors hemagglutinin (HA), the neuraminidase (NA) and M2 protein
• M1 – matrix protein lies beneath the lipid layer

Question 10

The virus core is comprised of the

Answer 10

• The virus core is comprised of the ribonucleoprotein (RNP) complex consisting of:
• Polymerase protein (PB1, polymerase basic 1)
• PB2 polymerase basic 2 • PA (polymerase acid)
• Nucleoprotein (NP)

• NEP/NS2 (_nuclear export protein/_non-structural protein 2)

Question 11

The genome has

Answer 11

• The genome has 6-8 segments of linear, negative sense, single stranded RNA

• 10-14.6 kb in overall size
• Genome segments have non-translated

regulatory sequences at both 5’ and 3’

Question 12

Because of the lipid envelope, influenza viruses are sensitive to

Answer 12

Because of the lipid envelope, influenza viruses are sensitive to heat (56°C/30 min.), acidic pH and lipid solvents

Question 13

Replication of Orthomyxoviruses

Answer 13

• The virus HA Molecule first binds to the cell surface receptors sialic acid containing receptor
• Different cells have different linkages of sialic acid to a galactose residue – host specificity
• Virus enters the cell through receptor- mediated endocytosis
• The low pH of endosomes triggers fusion of the virion envelope with endosomal membrane

Uncoating follows, releasing the RNA + nucleoprotein + polymerase proteins into the cytoplasm

The vRNA is immediately transported to the nucleus

The vRNA(-) serves as a template to produce mRNA

vRNA(-) is also used to produce full-length positive-sense RNA (cRNA(+)) which in turn is used as a template to produce vRNA(-)

The mRNA is transported into the cytoplasm where viral proteins synthesis occurs using the cellular machinery

Question 14

Virions are formed by

Answer 14

• Virions are formed by budding in the cell membrane

Question 15

Transmission

Answer 15

In aquatic birds the virus is shed in feces fecal-oral transmission is common

In poultry – ingestion and inhalation

In mammals – aerosol, droplets and

http://www.kingcounty.gov/healthservices/health/communicable/immunization/fluseason

fomites

Question 16

Thogotoviruses are transmitted by

Answer 16

Thogotoviruses are transmitted by ticks and replicate both in the ticks and

mammals

Question 17

Isavirus – may be transmitted

Answer 17

Isavirus – may be transmitted in water – gills being the important route

Question 18

Orthomoyoviruses can undergo

Answer 18

genetic shift- changes in antigenic setup due to reassortment of gene segments

or

genetic drift- changes in antigenic set due to point mutations(nucleotide substitution, deletion, or insertions)