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Composition of IAV

RNA (1%), Protein (73%), Lipid (20%) and Carbohydrate (6%).

Genome of IAV

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The Hemagglutinin

Receptor binding and fusion function

The major functions of the HA are the receptor-binding and fusion activities, but there
may also be a structural role for the HA in budding and particle formation.

The HA is a trimeric rod-shaped molecule (NA is tetrameric) with the carboxy terminus
inserted into the viral membrane and the hydrophilic end projecting as a spike away
from the viral surface
The overall amino acid sequence identity can be less than 50% (between 1918 and 2009),
the structure and functions of these HAs are highly conserved.

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How Influenza virus infect humans?

The cleavage sites present in HA vary between viral strains, and can affect tissue
tropism virus spread, and pathogenicity.
The HAs of highly pathogenic avian influenza viruses (HPAIV) of subtypes H5 and H7
contain a multibasic cleavage site (consensus sequence R-X-R/K-R) which is cleaved by
ubiquitous proteases such as furin or PC5/6, supporting systemic infection with an often
fatal outcome

HAT (Human airway trypsin-like protease) and TMPRSS2 (transmembrane protease serine
S1 member 2, also known as epitheliasin) are present in human airway epithelial cells
and have been shown to be capable of cleaving HAs having a monobasic cleavage site.

TMPRSS2 and the related protease TMPRSS4 have been reported to cleave the HA of the
1918 H1N1 virus at a monobasic cleavage motif.

Antigenic determinants
The formation of neutralizing antibodies.

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Mechanism of Entry

Influenza viruses require a low pH to initiate fusion and are therefore internalized by
endocytic compartments. There are four internalization mechanisms:
(a) via clathrin-coated pits;
(b) via caveolae;
(c) through nonclathrin, noncaveolae pathways;
(d) through macropinocytosis

The uncoating of influenza viruses in endosomes is blocked by changes in pH caused by

weak bases (e.g., ammonium chloride or chloroquine) or ionophores (e.g., monensin).
Effective uncoating is also dependent on the presence of the M2 protein, which has ion
channel activity.

Amantadine and Rimantadine inhibit replication immediately following virus infection

PATHOGENESIS IN HUMANS

Infect superficial cells of the respiratory tract

Alveolar macrophages and dendritic cells can be infected

The site of optimal growth in the respiratory tract for influenza viruses is, in part,
determined by the prevalence of the Siaa2,3Gal or Siaa2,6Gal receptors

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In children, virus can be found for up to 13 days after the onset of symptoms.

In immunocompetent patients, the A(H1N1)pdm09 virus is typically shed from

the day prior to the onset of symptoms to 5 to 7 days after the onset of illness

In school children (median age, 8 years), A(H1N1)pdm09 virus was isolated for a
median 2 days after fever resolution.

Oseltamivir treatment within 48 hours of symptom onset significantly reduced the

duration of shedding.

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Pathology

Infection induces changes throughout the respiratory tract, but the most clinically
important pathology develops in the lower respiratory tract

Acute diffuse inflammation of the larynx, trachea, and bronchi are observed with
mucosal inflammation and edema.

Desquamation

Infiltration of neutrophils and mononuclear cells.

Influenza virus–specific antigen is present in alveolar epithelial cells

Necrotizing changes may occur with rupture of alveoli and bronchiole walls.

Complete healing of the epithelial damage takes up to 1 month.

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Clinical Features

Range: Asymptomatic infection to primary viral pneumonia that rapidly progresses

to a fatal outcome

Symptoms: abrupt, with headache, chills, and dry cough, which are rapidly followed
by high fever, myalgias, malaise, and anorexia. Substernal tightness and soreness
can accompany the cough.

Prominent sign of infection is fever that often peaks within 24 hours at 38C
to 40C.

The elderly can have high fever, lassitude, and confusion without respiratory signs.

Conjunctival inflammation and excessive tearing may occur.

Illness is more frequent and more severe in cigarette smokers

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In children the intensity is higher.

Otitis, croup, pneumonia, and myositis are more frequent in children than in
adults.

Influenza A virus infection has been shown to exacerbate asthma.

Children (especially those younger than 3 years) have a higher incidence of

gastrointestinal manifestations such as vomiting and abdominal pain.

Infection of neonates can be life threatening

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