2. Family Orthomyxoviridae
• Enveloped virus
• ss RNA
• Affinity for mucous, hence name.
• Haemagglutination.
• Two class
Orthomyxovirus
Paramyxovirus
3. Orthomyxovirus v/s Paramyxovirus
Features Orthomyxovirus Paramyxovirus
Size 80- 120 nm 100- 300 nm
Shape Mostly Spherical/
Filamentous
Pleomorphic
Genome Segmented, 8* segments Single piece
Nucleocapsid 9 nm 18 nm
Site of RNP synthesis Nucleus Cytoplasm
Genetic recombination Common Absent
DNA dependent RNA
synthesis
Necessary Not required
Rate of antigenic variations High Low
Hemolysins Absent Present
*Exception: Influenza C contains 7 pieces.
4. Influenza virus
• Enveloped.
• ss RNA (Negative sense)
• 80- 120 nm
• 3 Serotypes:
• Influenza A (Human and animals)
• Influenza B (Human only)
• Influenza C (Human)
7. Influenza virus:
Antigenic classification
• Based on Nucleocapsid and M proteins 3 serotypes:
– Influenza A, B and C
• Based on HA and NA: Subtypes:
• 16 HA (H1 to H16)
• 9 NA (N1 to N9)
• Human Influenza virus:
– H1, H2 and H3
– N1 and N2
4 structural antigens:
1. Internal/ Nucleocapsid (RNP/ Ribonucleoprotein)
2. M Protein of Viral envelope (M1 and M2).
3. Haemagglutinin (HA)
4. Neuraminidase (NA).
3 Polymerase peptides:
1. PA
2. PB1
3. PB2
8. Influenza virus:
Serotypes and subtypes
Influenza virus
Serotype A
(Human and
animal)
• Subtype A1 (H1N1)
• Subtype A2 (H2N2)
Serotype B
(Only Human)
Serotype C
(Mostly Human)
9. Influenza virus:
Important Antigen
• Haemagglutinin:
– Great antigenic variations.
– Two glycoprotein chains (HA1 and HA2)
– Present as spikes
– Responsible for haemagglutination (with Fowl RBCs)
• Neuraminidase:
– Enzyme, a glycoprotein.
__________________________________________________________________
• Antigenic variations:
Antigenic drift
Gradual and sequential
Due to Mutation in both HA and NA
Responsible for periodic endemic.
Antigenic shift
Major and sudden change.
Due to gene reassortment or gene recombination.
Responsible for Pandemics and major epidemics.
10. Influenza virus:
Pathogenesis
• Mode of spread: Airborne
• Incubation period: 1- 4 days
• Entry: Respiratory tract
• Attached with respiratory epithelium.
• Neuraminidase lyse mucous membrane leads to Sloughing off
epithelium (vulnerable to secondary bacterial infection)
• Symptoms: Common cold to fulminate pneumonia. (fever, chills,
sore throat, cough, respiratory distress)
• Uncomplicated pneumonia resolve in 7 days.
• Extrapulmonary complications: (Rare)
– Guillain Barre syndrome.
– Reye’s syndrome (Due to Asprin use)
11. Influenza virus:
Lab diagnosis
Sample collection:
– Nasopharyngeal swab
– Nasal swab
– Serum
– BAL
Diagnosis:
1. Microscopy:
Demonstration of viral antigens: Direct Immunofluorescence (IFA).
Rapid method.
2. Isolation (cultivation) of Viral particles: (Mostly for research purpose)
Useful in first 2 to 3 days of infection
i. Egg inoculation: Amniotic cavity of 11 to 13 days old chick.
ii. Tissue culture: Primary monkey kidney, MDCK
iii. Animal inoculation : Mice
12. Influenza virus:
Lab diagnosis
3. Serology:
CFT (Complement fixation test)
Haemagglutination inhibition test
4. Molecular testing: RNA amplification followed by RT PCR ???
13. Influenza virus:
Epidemiology
• Influenza type A: Epidemic and Pendemic
• Influenza type B: Sporadic epidemic
• Influenza type C: Inappropriate infection
• Pandemic originates from reservoir animals or avians due to Antigenic shift
(Gene…………..?)
• Major pandemic:
– 1918- 19: 20 million deaths
– 1957: H2N2: From China
– 1968: H3N2: From Hongkong
– 1977: China and Russia: Red flu
– Swine flu: H1N1
• Originated: April 2009: Mexico and USA.
• WHO declares end of pandemic: 10 August, 2010.
– Avian Influenza: H5N1: 1997: Only bird to bird transmission, No human to human
transmission.
14. Influenza virus:
Prophylaxis
Immunoprophylaxis:
• Inactivated vaccine:
– Includes Subunit vaccine (only HA or NA)
– Only circulating antibody develops
– One year protection.
• Live vaccine:
– Develops local (secretary IgA) and circulatory antibodies.
Chemoprophylaxis:
• Rimantidine or Amantidine tablet (block M2 Protein)
Treatment:
• Drug: Ostelamivir (tamiflu) or Zanamivir