Describing Influenza Virus regarding Structure, Pathogenesis , Clinical significance, Laboratory diagnosis, and Antigenic variability of influenza viruses

1. Influenza Virus
Bilal Sami Al-Mosheqah

2. Learning Objectives
Influenza Virus
Clinical significance
Pathogenesis
Structure
Laboratory diagnosis

3. Influenza Virus
spherical, enveloped viruses containing a segmented , negative-strand RNA genome
Family : Orthomyxoviridae comprises :
I. Influenzavirus A: infect humans, horses, pigs and other
II. Influenzavirus B: infect humans only
III. Influenzavirus C: infect humans and pigs
Two types of spikes project from the surface:
One is composed of H protein and the second of N protein
 Influenzavirus C has a different type of surface protein
called Hemagluttinin-estrese-Fusion
The M (matrix) proteins underlie the viral lipid membrane.
The RNA genome, located in a helical nucleocapsid, is composed of eight
distinct segments of RNA (influenzavirus c has 7 segments) each of which
encodes one or more viral proteins

4. A nuclear export protein (NEP) is also associated with the virus.
hemagglutinin (HA) is a trimer
neuraminidase (NA) is a tetramer
M2 ion channel is a tetramer
The matrix protein (M1)
underlies the plasma
membrane–derived lipid
envelope
Structure
• present within the virion
particle is the viral RNA
dependent RNA
polymerase enzyme
uncoating of the virion

5. Structure
Hemagglutinin (HA)
18 serotype : only H1, H2, H3, and H5 are human
Bind to sialic acid (cell surface receptor)
Fusion of envelope with the membrane
Initiate infection
Neuraminidase (NA)
11 serotype : only N1 , N2 are human
Cleaves sialic acid residues
Promotes the release of progeny viruses and the spread of the virus
from the host cell to uninfected surrounding cell
This enhances the ability of the virus to gain Access to the respiratory
epithelial cells
Degrades the protective layer of
mucus in the respiratory Tract

6. The inhibition of which one can prevent the disease ?
zanamivir and oseltamivir

7. Viral replication
 the synthesis of influenza virus mRNAs and the replication of the viral genome occur in the nucleus
Viral entry into the cell
o Attaches to sialic acid residues on host cell glycoproteins or glycolipids
o Entry then occurs via receptor-mediated endocytosis
 Both the attachment and the fusion functions are associated with the H protein
o Enters the cell in vesicles and uncoats within an endosome

8. o Synthesis of the eight mRNAs occurs in the nucleus
Viral replication
Synthesis and translation of viral mRNAs
o The cap is obtained from cellular nuclear RNAs in a process called “cap snatching.”
o Most of the mRNAs move to the cytoplasm, where they are
translated
a methylated guanosine “cap” is required
o Some of the viral mRNAs remain in the nucleus, where they serve as the template
for the synthesis virions
?

9. Viral replication
Assembly and release of influenza virus particles
o Two newly synthesized proteins, Nucleoprotein protein and matrix protein, bind to the progeny
RNA genome in the nucleus, and that complex is transported to the cytoplasm
o The helical ribonucleoprotein assembles in the cytoplasm
o Matrix protein mediates the interaction of the nucleocapsid with the envelope
o Virion is released from the cell by budding from the outer cell membrane at the site where
the hemagglutinin and neuraminidase are located
o The neuraminidase releases the virus by cleaving neuraminic acid on
the cell surface at the site of the budding progeny virions

11. The viral genome is imported into
the nucleus through nuclear pores
Receptor-mediated
endocytosis of the virus

12. EPIDEMIOLOGY
Adults are infectious from 1 day before symptoms begin through approximately 5 days
after onset of illness
Rates of influenza infection are highest among children
Rates of serious illness and death are highest among persons aged 65 or older and persons of any
age who have medical conditions that place them at high risk for complications from influenza
Overall mortality rate is about 1%.
Epidemic flu is cyclic and is usually caused by virus types A or B
Epidemics of type a occur every 2–3 years.
Epidemics of type b occur every 4–6 years
Transmitted by airborne respiratory droplets

13. Pathogenesis
If a susceptible person inhales droplets containing the
influenza virus, the virus attaches to the epithelial cells
lining the respiratory airways as well as to the nasal
turbinates
 Virus replicates in the cells, causing :
 Desquamation of ciliated epithelium
 Edema
 Hyperemia
 Congestion
 Increased secretions
 Viremia rarely occurs.
 Pneumonic complications without secondary bacterial
infections can occur; however they usually are due to a
secondary infection with bacteria (commonly S aureus).
Neuraminidase degrades
the protective mucus layer
Immunity depends mainly IgA in the respiratory tract.

14. Incubation period : 24 to 48 hours
Clinical finding:
o Sudden fever , Severe myalgias (muscle pains)
and headache (IFN/Cytokines)
o Non productive cough
o Vomiting and diarrhea (Rare)
o Spontaneous resolution in 4-7 days
o Pneumonic complications without secondary bacterial infection
Clinical significance
Reye’s syndrome
characterized by encephalopathy and liver degeneration, is a rare, life-threatening complication in
children following some viral infections, particularly influenza B and chickenpox.
 Aspirin given to reduce fever in viral infections has been implicated in the pathogenesis

15. Influenza A viruses undergo both shift and drift
Influenza B viruses only undergo drift in their H and N antigens
Antigenic variability of influenza viruses
Antigenic drift
Minor antigenic changes in H and N proteins that occur each year
Does not involve a change in the viral subtype.
Antigenic shift
More dramatic change in the antigenic properties of the H and/or N
proteins and a change in subtype, for example, from H1N1 to H3N2
Antigenic shift occurs only infrequently, perhaps every 10 or 20 years

16. Laboratory diagnosis
A definitive diagnosis cannot be made on clinical grounds except in an epidemic situation
 Isolation of virus from nasopharyngeal washings in culture is the gold standard, but is difficult and time
consuming
 Rapid tests are also available in which viral antigens (neuraminidase or nucleoprotein) can be detected in
nasopharyngeal swab specimens
 Detection of viral RNA by RT-PCR is sensitive and specific

17. Properties Enveloped RNA virus with segmented negative-strand RNA genome
Three types of influenza virus A, B , C , A and B associated with epidemics
Contain surface protein haemagglutinin (HA) , neuraminidase (NA)
Infect ciliated columnar epithelial cells of respiratory tract
Epidemiology Person to person (airborne or by contact with contaminated surfaces)
Mortality rate is about 1%.
Adults are infectious from 1 day before symptoms begin through approximately 5 days after
onset of illness
Clinical significance Influenza (Sudden fever , Severe myalgias (muscle pains) and headache
Spontaneous resolution in 4-7 days
Diagnosis Enzyme immunoassay (EIA)
Nucleic acid amplification test (naats)
RT-PCR
Management Two neuraminidase inhibitors (NIS):
Zanamivir and oseltamivir, have been licensed for therapeutic use in influenza A and B infections
Summary

18. Any Question

19. Reference
Warren E. Levinson (2014) Review of Medical Microbiology and Immunology, 13th edn., New
York, United States: McGraw-Hill Education - Europe.
Neal R. Chamberlain ( 2009) Medical Microbiology: The Big Picture, New York, United States:
McGraw-Hill Education - Europe.
Richard A. Harvey , Cynthia Nau Cornelissen (2012) Lippincott Illustrated Reviews:
Microbiology, Third edn., Philadelphia, United States: Lippincott Williams and Wilkins.