Lecture Notes on Influenza viruses

1. ORTHOMYXOVIRIDAE
DR. IRIAGBONSE OSAIGBOVO

2. RNA VIRUSES
Picornaviridae
Caliciviridae
Reoviridae
Paramyxoviridae
Rhabdoviridae
Orthomyxoviridae
F
Filoviridae
Arenaviridae
Bunyaviridae
Retroviridae
Togaviridae

3. Orthomyxoviridae
Enveloped
Single stranded RNA viruses of humans and other animals
Cause highly contagious airborne respiratory illness- Influenza
Devastating pandemics
Influenza viruses- A,B, C

4. Virology
Genome- single stranded, negative sense segmented RNA
Each of the 8 segments code for a single protein
Helical symmetry
Lipid envelope derived from host cell
Glycoprotein spikes embedded in envelope- haemagglutinin(HA), neuraminidase
(NA)

5. Influenza virus

7. Haemagglutinin, Neuraminidase
Mediate viral entry and exit from hot cells
HA binds to sialic acid residues on target cells to initiate infection
Neuraminidase degrades mucous layer to expose these residues
Post replication, neuraminidase cleaves sialic acid to facilitate release of progeny
viruses

8. Haemagglutinin, Neuraminidase
Key antigenic components- variation in their sequence is the basis of subtyping of
Influenza viruses
HA is the major antigen against which protective neutralizing antibodies are
formed
NA is an important drug target- Inhibitors include Zanamivir, Oseltamivir

9. Functions of other viral proteins
Matrix proteins, M1, M2
M1- structural integrity, located between nucleoprotein and envelope
M2- ion channel. Essential for uncoating
Non-structural protein,NS1

10. Replication
Attachment- Haemagglutinin binds to sialic acid
Uncoating- Facilitated by low pH in endosomes, entry of protons via M2 ion
channels
Transcription- Important steps in the nucleus( unlike most RNA viruses). Viral
RNA polymerase transcribes all genomic segments to mRNA
mRNAs move to cytoplasm for translation to protein

11. Replication (contd)
Assembly of nucleocapsid in nucleus
Release by budding through membrane embedded with glycoproteins, HA,NA

13. Pathogenesis
Airborne respiratory droplets are transmitted to the upper airway
Primary infection occurs marked by multiplication in ciliated columnar epithelial
cells: impaired ciliary function
Cytotoxic and immunologic damage results in desquamation
Secondary bacterial infection may follow
Localised disease- viraemia does not occur

14. Clinical features- Uncomplicated
Incubation period- 24 to 48 hours
Sudden onset of fever, myalgia, headache, sore throat, cough
Symptoms resolve in 7-14 days

15. Clinical features- Complications
Occur in elderly, children, people with underlying medical conditions, DM, cancer
Primary viral pneumonia
Secondary bacterial pneumonia due to S.aureus, H.influenzae
Reye’s syndrome characterised by encephalopathy and liver degeneration
associated with aspirin use in childeren

16. Laboratory diagnosis
Diagnosis mostly clinical but lab. Confirmation may be necessary, especially in
outbreaks since many viruses can cause similar respiratory illness
Useful specimens- nasal and throat swaps, sputum
Isolation of virus in cell culture
Identification of viral antigens
RT-PCR to detect viral RNA
Serology

17. Treatment/Prevention
Treatment mostly symptomatic
Drug treatment effective when given early; reduces duration and severity
Useful for high risk patients prone to complications
Neuramanidase inhibitors_ Oseltamivir, Zanamivir
M2 ion channel blockers e.g Amantadine, Rimantadine

18. Prevention- Vaccination
Annual vaccination for at risk groups and health care practitioners
Modified annually to include the most prevalent strains
2 types- inactivated (killed) vaccine + live-attenuated vacine

19. Antigenic Shift and Drift
Influenza viruses are genetically labile with resulting variations in HA, NA
Capacity to cause seasonal outbreaks and pandemics
Antigenic drift- Minor changes resulting from point mutations; frequent;result is
seasonal outbreaks
Antigenic shift- Major change based on reassortment of genomic segments
between two strains

20. Antigenic shift
Reassortment of segments
Involves coinfection of a host by two strains of Influenza A virus
Host, or mixing vessel presumed to be pigs (swine)
Results in virus that is more virulent than individual strains
Causes pandemics- Spanish flu pandemic of 1918(H1N1)

21. Influenza pandemics
Major pandemics:
1918 (H1N1)
1957(H2N2)
1968(H3N2)
Smaller pandemics- 1947,1976, 1977, 2009 (H1N1)

22. Avian Influenza
Zoonosis
Acquired from direct contact with diseased poultry
More severe than human influenza- attacks lower respiratory tract
No sustained human to human transmission
Currently no vaccine