Influenza. Respiratory System. Ziegler. 10.28.09. Katelyn Rogers.
Definition: is a localized infection of the respiratory tract, further down then the larynx. Secondary bacterial infections more
likely.
Influenza virus = Orthomyxovirididae:
Size (nm)
100
Enveloped
Yes
Capsid Symm
Helix
Nucleic Acid
RNA
Class
V
Form
Ss
Seg
8
Genes
10
KB:
13.6
Influenza Viruses: Types based on existing nucleocapsid antigens (nucleoprot). Segmented, enveloped with 8 helical
nucleocaspids each containing difft negative sense ssRNA viruses. H protein interacts w/ cellular rec to initiate infection.
Type A
Type B
Type C
Cause potentially severe infections
Cause potentially severe infections
Humans, pigs, birds, horses, & marine mammals infected.
Only type that undergoes antigenic shift
Undergoes antigenic driftreassortment
Undergoes antigenic driftreassortment
Reassortment: Because segmented, any mixture of these 8 helical nucleocapsids can get into one cell during replication.
Proteins in the influenza virurses:
Polymerases (RNA)
Hemagglutinin (Hs)
Neuraminidase
M2 protein
The viral attachment protein
Active in env fusion to host cell Forms a proton chl
memb & aids virus release
necessary for replication
Seg 1,2,3
Seg 4
Seg 6
Seg 7
Virus enveloped glycoprotein
Viral env enzy that hydrolyses Env prot that fxns as an ion
sialic acid residues
chl, activated by low pH of
endosome to allow viral
uncoating.
15 difft Hs of influenza A in
9 Influenza A virus N subtypes
human & other species. H1-4
mainly in humans.
Anti-H abs neutralize virus
Anti-H abs help inhibit spread Binds antivirals amantadine
infectivity
of virus & virus release from
& rimantidine that inhibit
cells
virus replictn (incoding)
Replication: Uncoating involves the ion chl of the viral M2 protein. Atypical minus strand RNA virus bc REPLICATES IN
NUCLEUS since it needs RNA pol II to make m-RNAs. (normally replicate in cytoplasm when RNA virus)
Antigenic drift:
RNA mutations more freq than DNA mutations.
Mutation in hemoglutininchange in folding of H1 for eg (doesn’t become
another type H2 for eg).
This small change cause our abs to not be as effective at neutralizing the
virus. This is why we get annual seasonal flu shots. Drift occurs each
year.
Antigenic Shift:
Depends on random assortmentforms hybrid viruses.
May switch from human H1 to swine flu in H4. It is a completely
new hemaglutinin. Normally pandemics are due to shift.
Disease: Influenza (Orthoomyxoviridae)
Symptoms: Fever, chills, aches, nausea, sore throat, cough, & general malaise.
Complications: Secondary bacterial infections, pneumonia, & Reye’s Syndrome (follows Type B)
Vaccines:
Seasonal Influenza (Caused by antigenic drift)
Trivalent vaccines (2 A and 1 B)
Two types of inactivated vaccines
-split (chemically txd virions) – Afluiria, FluLaval, Fluxone, & Fluarix
-subunit (purified H & N glycoproteins) –Fluvirin
Inactivated 2009-10 Vaccines (for seasonal flu):
-Inactivated trivalent vaccines contain 15 micrograms H of the following strains (guessed by the gov):
-A/Brisbane/59/2007 (H1N1)
-A/Brisbane/10/2007 (H3N2)
-B/Brisbane/60/2008
One live attenuated vaccine- Flumist
Oral mist
Adv: generates sec IgA
Disadv: could revert
Age consideration
2009-2019 Live, Attenuated Vaccine
Trivalent vaccine contains 106.5-7.5TCID50 in O.5 ml of live attenuate virus ressortments of masotr
done viruses (A/Ann Arbor/6/60 & B/Ann Arbor/1/66) & the recommended vaccine strains
-Six gene segs form master donor viruses & H & N gene segs from recommended wild
type stains.
Antivirals:
Zanamivir (Relenza) & Oseltamivir (Tamiflu)
Amantidine & Rimantidine
-inhibit influenza A & B virus neuraminidase.
-bind to M2 protein
-Zanamivir used for tx; Oseltamivir used for prophylaxis & tx.
-prevent acidification of endosomal vacuolesinhibits virus uncoating.
-H1N1 Oseltamivir-resistant strains have been identified; ~10% in US
-can be used for tx & prophylaxis of Influenza A virus infxns.
in 07-08 season.
2009 H1N1 Flu (Swine Flu)
-April 2009 – Novel influenza A (H1N1) virus was diagnosed as
causing illness in USA (not a normal pandemic with a shift, rather drift
to a major change in folding of the hemaglutinin & neuraminidase)
-July 11, 2009 WHO declares WW epidemic.
-Signs & symptoms of the dx are ~ to seasonal flu.
-Highest incidence of infxn is among young persons 5-24 yo.
-Incidence of hospitalization is highest in young children < 4yo.
-Monovalent Vaccine:
Both a live attenuated & an inactivated vaccine are
available.
Target groups have been identified.
Antivirals:
-Both Oseltamivir (Tamiflu) & Zanamivir (Relenza) can be used, but
are most effective early in the disease.
-Should only be used for those w/ greater chance of complications or
are very sick.
-Tamiflu comes in liquid or capsules & can be used for small children.
-Relenza is an inhaled powder approved for children >7 yo.
Avian Influenza A (H5N1)
-Poultry virus of which some strains infect humans.
-Almost 300 human cases reported (>1/2 died)
-Inactivated vaccine for high risk person contains the
A/Veitnam/1203/2004 strain and requires two 90 mcg. Does (im)
for effect.
-USA has a National Pandemic Influenza Response &
Preparedness Plan
-No evidence of reassortment into human Influenze A.
Avian Influenza A (H9N2)
-Several cases of human infection w/ avian H9N2 virus occurred
in Hong Kong & Southern China in 1999.
-The disease was mild & all patients made a complete recovery.
-No evidence of reassortment into human Influenze A.
Questions:
1. Which of the following types of influenza virus undergo antigenic drift?
a. Type A
b. Type B
c. Type C
2. T/F: Antigenic drift leads to a pandemic.
3. Types of Influenza are based on the following?
a. Nucleocapsid
b. Hemoglutitin
c. Neuroaminidase
d. M2 Protein
4. Which of the following assists in envelope fusion to the host cell membrane & aids in virus release? What is
hydrolyzed in this process?
a. Nucleocapsid
b. Hemoglutitin
c. Neuroaminidase
d. M2 Protein
5. Which antivirals does the M2 protein bind to inhibit replication?
6. Which of the following vaccines is not used for the seasonal flu?
a. Trivalent vaccines – 2A & 1B
b. Monovalent vaccines
c. Avian Influenza A vaccine
7. Which of the following antivirals can be used to treat both seasonal & 2009 H1N1 influenza? What is their
mechanism? Which one is used for prophylaxis of seasonal flu?
a. Amantidine
b. Oseltamivir
c. Rimantinde
d. Zanamivir
Answers:
1. A
2. F, Antigenic shift normally leads to a pandemic (2009 H1N1 is not a normal pandemic, because it is caused by a
“large” drift making the seasonal flu vaccine completely helpless against it.)
3. A
4. C, sialic acid.
5. Amantidine & Rimantidine
6. B & .
7. B & D. Inhibit influenza A & B virus neuraminidase (not just Influenza A like Rimantidine & Amantidine). B.