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Spanish Flu characteristics

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Young adults
Rapid death:
Influenza-> pneumonia->cyanosis->death
Mortality rate: 2.5% (vs 0.1%)
Average Life Span US:-10y!

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causes worldwide epidemics (pandemics) of influnza

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Influenza A virus

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causes major outbreaks of influenza

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Influenza B virus

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causes mild respiratory tract infection, but not cause outbreaks of influenza

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Influenza C virus

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Influenza virus genome

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segmented single-stranded RNA genome, a helical nucleocapsid, and an outer lipoprotein envelope.
-eight unique negative-sense RNA nucleocapsid segments.

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How is influenza transmitted?

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by airborne respiratory droplets.

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The ability of influenza A virus to cause epidemics is

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dependent on antigenic changes in the viral glycoproteins: hemagglutinin (HA) and neuraminidase (NA)

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viral attachment protein and fusion protein; it elicits neutralizing, protective antibody responses

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Hemagglutinin

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How does influenza virus replicate?

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Influenza transcribes and replicates its genome in the target cell nucleus but assembles and buds from the plasma membrane.

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these drugs inhibit an uncoating step and target the M2 (membrane) protein for influenza A only.

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amantadine and rimantadine

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these inhibit the NA protein of influenza A and B so entry into host is prevented.

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zanamivir and oseltamivir

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What is the advantage provided by the influenza genome?

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promotes genetic diversity caused by mutation and reassortment of segments on infection with two different strains

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Influenza Virus A can infect

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humans, mammals, and birds (zoonosis).

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Surface Proteins of Influenza Virus A

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: HA, NA, M2

Matrix: M1

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Nucleocapsid Proteins of Influenza Virus A

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: NP 8 (-) ss RNA, PB1, PB2, PA

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Non structural Proteins of Influenza Virus A

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NS1, NS2

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Influenza virus uncoating happens in the

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cytoplasm

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Systemic symptoms caused by Influenza A and B are due to the

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Interferon and lymphocyte response.

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Local symptoms caused by influenza A and B are due to

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Epithelial cell damage, including cilliated and mucus secreting cells

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Bacterial Superinfections can occur in patients with Influenza why?

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Loss of natural barriers and exposure of binding sites on epithelial cells

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Antibody memory is developed in patients who had influenza. What are the antibodies against?

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HA and NA proteins

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Major antigenic changes to HA and NA of Influenza A due to

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Antigenic shift

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Minor antigenic changes to HA and NA of Influenza A due to

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Mutation:drift. Influenza B only undergoes minor changes

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Influenza virus A and B virions are inactivated by

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Dryness, Acid and detergents. Coinfection with animal and human strains can generate unique virus strain

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What kind of environment does influenza prefer?

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Cool and less humid atmosphere (winter heating season)

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Who is at risk of influenza?

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Seronegative people
Adults:present with classic flue
Children: asymptomatic and then severe respiratory tract infection.
Greatest risk: Eldery, immunocompetent, Asthma, heart problems patients

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Prophylaxis as well as early tx of influenza is by

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drugs like amantadine

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Killed and live vaccines contain

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Predicted yearly strains of influenza A and B

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Fever, malaise, myalgia, sore throat, and nonproductive cough are symptoms of

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Acute influenza infection

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Fever, malaise, myalgia, sore throat, and nonproductive cough and GI symptoms are signs of

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Acute infection in children

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What is the best method to detect influenza?

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PCR and Elisa

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HA1(aa 1-328) mediates

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viral attachment to sialic acid (SA)

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HA2(aa 329-539) mediates

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endosomal membrane fusion

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Under low pH conditions, HA interacts with

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vesicle and leads to virus release inn cytoplasm

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Sialic Acid alpha2,3 linkage
Preference

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avian virus

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Sialic Acid alpha2,3 linkage localization

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Gastrointestinal tract (avian)
Lower respiratory tract (humans)

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Sialic Acid alpha 2,6 linkage
Preference

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: human virus

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Sialic Acid Sialic Acid alpha 2,6 linkage location

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Upper respiratory tract
(humans)

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what is Neuriminidase

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Catalyzes the removal of terminal sialic acid (Neu5Ac) from oligosaccharide chains

Facilitates virus the egress from infected cells

Inhibition of NA limits the establishment and/or progression of infection

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Neuriminidase inhibitors

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Oseltamivir, zanamivir.

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Oseltamivir [Tamiflu] characteristics

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Given orally
Absorbed from the gastrointestinal tract, converted by hepatic esterases to the active form of the compound.

Half-life is 6-10 hours.

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Zanamivir [Relenza) characteristics

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Given intranasally
,Poor bioavailability (administered intranasally)

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a naturally occurring substance found in plants like Chinese star anise, ginkgo, spruce, pine and fir trees

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oseltamivir from shikimic acid

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Adamantanes function

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act by blocking the ion channel function of the virus protein M2

Not effective against influenza B viruses

Clinical use is limited by side effects