Download Influenza virus:

College of Medicine
Microbiology
RNA viruses
--------------------------------------------------------------------------------Influenza virus:
General properties:
 Shape of virus is spherical, symmetry of nucleocapsid is helical.
 Viral genome is segmented ssRNA(7– 8 segments).
 Enveloped(bi-layer membrane)
 Spiked: 2 types of proteins:H(Hemagglutinin) and N( Neuraminidase).
Classification and nomenclature:
Influenza virus classified into three types according to group-specific
antigens (nucleocapsid antigens): influenza A, B and C.
Influenza type A and B contain 8 segments, while influenza type C has 7
segments of ssRNA.
The influenza type A (only) can be divided into subtypes(serotypes)
according to species-specific antigen( H and N antigens). So far, 15
subtypes of H (H1-H15) and 9 subtypes of N(N1-N9).
Standard nomenclature system for influenza virus include; type, host,
geographic, strain number, and year of isolation. For example:
A/swine/Iowa/15/30(H1N1).
Source and transmission:
 Host range : Influenza A has broad host range capable of infecting
human, swine, horses ,chicken and birds(aquatic birds). Influenza B
and C host range is limited to human only.
 Infected humans are main reservoir of infection. The virus transmitted
from person to person by air-borne respiratory droplets and by contact
with contaminated materials of patient.
 Avian influenza virus(influenza-A) cause bird flu in domestic poultry
birds, subtype H5N1can be transmitted from birds to humans, H5N1
enable to kill half of people who become infected. Fortunately avian
virus was poorly transmissible to human.
Antigenic variation:
Because viral genome is segmented, genetic reassortment can occur during
viral replication. The reassortment could lead to emergence of new human
virus(new strain), the progeny of which will contain a mixture of genome
segments from human and from animal strain. Therefore antigenic variation
can occur due to mutation in sequence of amino acids in proteins of H and N
. The mutation leads to change in antigenic nature of H or N or both
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resulting new strains that non-identified by immune system(escape from
immune recognition).
Two types of variation are known:
 Antigenic shift( complete change in H or N or both). This can only
occur with influenza type A because it has wide host range , when two
viruses co-infect the same cell (one human strain and another animal
strain), during viral replication ,the RNA segments can be mispackaged into another virus and release new strains. Antigenic shift is
responsible for influenza pandemics.
 Antigenic drift(partial changes). This occurs in type A and B. It
involves minor changes affecting H or N, not both. It is responsible
for influenza epidemics.
N.B: Antigenic change not appears in birds, perhaps because of their brief
life span.
Antigenic variation of envelope proteins H and N is responsible for epidemic
and pandemic diseases. Influenza A cause major epidemic
disease(pandemic) with significant mortality. Influenza B cause sporadic and
periodical epidemic disease, usually milder than influenza A. While the
influenza C cause minor (mild), sub-clinical disease, because it stable
antigenic and lack neuraminidase gene (the gene is located on segment
which the type C hasn’t it).
Pathogenesis:
 Virus is limited to ciliated epithelial cells of respiratory tract, leading
to cell death. Denudation of respiratory epithelium causes acute
inflammatory response and renders the individuals to bacterial superinfections.
 N antigen facilitates infection by reducing the viscosity of mucus
lining by cleaves neuraminic acid( the substrate covering mucosal
epithelial cells of respiratory tract) and disrupts the mucin barrier
,then exposing the cell receptor for virus absorption( H responsible
for absorption). H antigen can attach to receptor on epithelial cells
resulting in gulf of virus by endocytosis and in dumping of viral
genome into host cell.
 Within short time many cells in respiratory are infected and killed.
The virus replicates within nucleus of infected cell and result in shutoff of host cell protein synthesis by 3 hr. and new progeny viruses are
produced within 8-10 hr.s
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 The virus remains localized to respiratory, hence viremia does not
occur.
 Antibodies provide long-lasting immunity (not long life immunity)
against influenza infection.
C/F:
 IP(1-4 days) dependent upon size of dose and immune status of
human. Fever ,headache, nose secretion, anorexia, cough and
generalized myalgia(muscle pain) are most clinical features. If no
complication, the disease resolve in 2-7days.
 Complication of influenza ; individuals at greater risk for
complication include elderly and immunocompromised people, the
virus spreads to LRT , resulting in secondary infection such as
bacterial pneumonia caused by Strep.pneumoniae ,Staph.aureus or
Hemophilus influenzae .
 Other viruses; parainfluenza viruses are responsible for 10%
respiratory infections in children. They are classified into 4 types.
They cause influenza-like illness with croup.
Epidemiology:
 Influenza occurs primarily in winter months, when it and bacterial
pneumonia secondary to influenza cause a significant number of
deaths especially in older people. In southern hemisphere, eg. in
Australia and New Zealand , influenza occurs in winter months of
June through August.
 Influenza has been responsible for millions of infection worldwide.
Most cases due to type A. It is estimated 3-5 millions infected cases.
 Influenza occurs worldwide distribution (epidemics) . Influenza
outbreak occurs in wave. The period between epidemic wave of
influenza A tend to be 2-3 years, type B is longer 3-6 years .
Pandemic disease occurs every 10-40 years. Shift variants appear
every 10 years, whereas drift variants appear every year
(approximately).
 Global influenza infection(epidemic):
1889 H2N2
1900 H3N2
1918 H1N1(Spanish flu)
1947 H1N1
1957 H2N2(Asian flu)
1968 H3N2(Hong Kong flu)
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1977 H1N1(Russian flu)
1997 H5N1
1999 H9N2
2004 H5N1
2006 H5N1
2009 novel strain contains mixed genome (originated from bird as well
as from swine and human).
Lab.Dx:
 Virus is isolated from clinical specimen(nasal washings, gargles and
throat swabs) in cell culture.
 Detection of specific antibodies level over 2 weeks by serological
tests : CFT and ELISA
 Detection of viral nucleic acid by PCR.
 Detection of viral proteins.
Control methods:
a. Treatment:
 Amantadine and Rimantadine are used to prevent uncoating of
influenza A. Whereas Sanamavir (inhaled) and Oseltamivir (oral) are
inhibitors for neuraminidase in influenza A and B.
 Children given aspirin(salicylate) when they have influenza can
develop a severe liver and brain disease called (Reye syndrome).
Give acetaminophen for fever in children, no aspirin.
b. Prevention:
 Influenza virus vaccine (killed vaccine) has been used to prevent
infection, primarily influenza A and B. It given intramuscularly for
elderly and immunocompromised patients. Attenuated influenza A
vaccine (given intra-nasally ;spraying into nose ) is available for
healthy adults and children. Because the virus undergo antigenic
shift, the vaccine will not be effect in protecting against the new
subtypes of virus . Therefore, it becomes necessary to develop a new
vaccine as quickly as possible.
 Personal hygiene and avoid contact with patients.
 Avian virus was controlled by destroying poultry.
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