2. Introduction
Orthomyxoviridae is a family of RNA viruses. It
includes seven genera: Influenzavirus A,
Influenzavirus B, Influenzavirus C, Influenzavirus D,
Isavirus, Thogotovirus, and Quaranjavirus. The first
four genera contain viruses that cause influenza in
vertebrates, including birds, humans, and other
mammals.
4. General classification
Orthomyxoviruses are large, enveloped virions with
helical nucleocapsids.
Negative sense, segmented RNA genomes.
Pleomorphic: laboratory strains are often spherical,
whereas clinical strains are often filamentous.
Replicate in the nucleus.
Upon budding, the host cell is killed.
5. Conti....
Influenza viruses A, B, and C are pathogenic in
humans
Influenza A and B are responsible for most illnesses
and epidemics.
Influenza A also infects non-human mammals and
birds, which facilitates zoonotic infections.
6.
7. Antigenic changes:
– Minor changes include mutations, which can lead to genetic
drift and epidemics; both influenza A and B undergo these kinds
of changes.
– Major changes include re-assortment, which can lead to
genetic shift and pandemics; influenza A virus is associated with
pandemics.
– Reassortment occurs when viruses with segmented genomes
create a hybrid strain.
– An example of this is the H1N1 pandemic strain that arose in
2009; this strain contained genetic information from avian,
human, and swine influenza viruses.
Host immune response involves cytokine storms and
interferons that are largely responsible for the symptoms of the
flu.
8. Virion Components & Their Functions:
Nucleocapsid
Lining
– Matrix protein (M1) promotes virion assembly.
Envelope
– Membrane protein (M2) facilitates viral uncoating
and release from the host cell; it does so via formation
of proton channels that allow for acidification, which
is necessary for membrane fusion.
– Amantadine and rimantadine target M2 of
Influenza A, thus blocking viral uncoating.
9.
10. Virion Components & Their Functions:
Envelope glycoproteins
– Hemagglutinin acts as a viral attachment protein; it binds sialic
acid on epithelial cells (there are a couple of exceptions).
Also acts as a fusion protein, attaching the viral envelope to the host
cell membrane.
Elicits a neutralizing antibody response.
Subtypes determine the species and tissue type that the virion can
infect.
– Neuraminidase
Facilitates virion release from the host cell by cleaving sialic acid.
Anti-viral drugs zanamivir and oseltamivir act on neuraminidase to
block virion release.
Neuraminidase has other functions, which may include liquefaction of
the mucous covering of the respiratory tract.
12. Key steps of influenza pathogenesis:
The virus reaches the mucosal epithelia via
respiratory droplets.
– The virus can also be transferred to mucosal surfaces
via other mechanisms; for example, the virus can be
picked up from counters, keyboards, and other hard
surfaces, then transferred to the nasal mucosa from
the hands.
As showed earlier, the virus uses sialic acid
receptors on host epithelial cells to gain access to host
cells for replication.
13. Replication primarily occurs in the tracheobronchial
tree.
Infection triggers release and recruitment of
inflammatory cytokines, type 1 interferons, and pro-
inflammatory cells.
In turn, the adaptive immune system is triggered, and
T-cells are activated and antibodies are produced.
– These agents provide future protection against re-
infection by the same influenza strain.
14. Infected epithelial cells are destroyed by budding
virions, cytokines, interferons, and other anti-viral
agents.
– Destruction of epithelial cells also removes the
mucosa and cilia that would otherwise provide
a physical barrier against pathogens.
Symptoms of influenza include fever, headache,
cough, chills, muscle pain, sore throat, sinus
congestion, and others; again, indicate that these
symptoms are primarily caused by the host immune
response.
15.
16. Complications:
In some individuals, complications from the flu can be life-
threatening.
Pneumonia can result from viral infection or from secondary
bacterial infections.
Organ inflammation or failure can occur.
Sepsis.
Indicate that individuals at higher-risk for these complications
include those with compromised immune systems, particularly:
Very young children (under the age of 5)
Pregnant women and women less than two weeks' post-partum
Adults over the age of 65
17.
18. Diagnosis
Based on the symptoms
ElISA
Cell line culture
Immunodiffision
Heamagglutination
19. Host defense
Interferon appears in respiratory secretions shortly
after viral titers reach their peak level, and may play a
role in the subsequent reduction in viral shedding
T cells and antibody-dependent cell-mediated
cytotoxicity also participate in clearing the infection.
20. IgG antibody, which predominates in lower respiratory
secretions, appears to be the most important. The IgG
in these secretions is derived from the serum, which
accounts for the close correlation between serum
antibody titer and resistance to influenza. IgA
antibody, which predominates in upper respiratory
secretions, is less persistent than IgG but also
contributes to immunity.
21. Prevention & Treatment:
It is difficult to avoid the flu in part because individuals begin shedding
the virus before symptoms appear.
Flu vaccine is the best way to prevent the flu.
– Seasonal vaccines are tailored to protect against strains that are
predicted to be most common in a given season.
– Most are three component vaccines (aka, trivalent), which means they
protect against two strains of Influenza A and one strain of Influenza B.
– Four component (aka, quadrivalent) vaccines are also available; they
protect against the same strains as the trivalent vaccine and an
additional strain of Influenza B.
– The vaccines can prevent the flu or, if unable to provide complete
protection, they can reduce the severity of symptoms and the
likelihood of developing complications.
Patients with influenza may be given antivirals to reduce symptom
severity and the likelihood of complications
