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113 Cards in this Set

  • Front
  • Back
How is influenza transmitted?
respiratory epithelium
-so, virions that get into your respiratory tract
How many types of colds are there?
>200 different virures + Group A strep (bacterial)
Why do we catch more colds in the winter than in the summer?
Children in school
Why is a vaccine against the common cold impossible?
The more different antigens you put together into a single vaccine, the lower the mean geometric antibody titer response to any single component!
Is the cold endemic or epidemnic?
endemic
How is influenza easily distinguishable from the common cold?
-more serious illness
-can't get out of bed
How long is the influenza incubation period (to most severe symptoms)?
3 days
Name some symptoms of flu:
-headache
-malaise
-myalgias
-nasal obstruction + discharge
-throat pain
-cough
Is influenza endemic or epidemic?
epidemic
When did the 1986 Dallas flu epidemic peak?
in February
Over the course of history, what have been the two major killers, in terms of infectious diseases?
Influenza
Typhoid
What was the peak death rate of Spanish flu?
600 deaths/100 000
What is the term for a disease causing world-wide outbreaks?
pandemic
Is a pandemic necessarily severe?
no
How was Asian flu of 1957 spread around the U.S.?
by girl scouts
What was the case fatality rate of 1957 Asian flu?
0.5%
What was the case fatality rate of 1918 Spanish flu?
5%
What has been the case fatality rate of H1N1 of 2009, thus far?
0.05-0.1%
What does flu do to the trachea/respiratory tract?
-infects and kills cells of respiratory tract
-Kills goblet cells
-Kills ciliated cells next
-leaves only basal cells
-no more mucociliary defenses
Why do people tend to develop bacterial pneumoniae following flu?
Since the non-specific defense have been breached, a secondary infection can easily take place.
Which antibodies are generated against flu?
-anti-Hemagglutinin (HA)
-anti-Neuraminidase (NA)
both surface glycoproteins on the envelope of Influenza
In which species is Influenza A seen?
all mammalian and avian species
How many HA and NA families are there?
>16 HA
11 NA
Which strains of influenza are in the typical seasonal vaccine?
H3N2
H1N1
If you got the flu vaccine last year, are you immune to this year's flu?
No!!
Which are the two most recent flu epidemics after 1918 and prior to 2009?
1957 - Asian flu - H2N2
1967 - Hong Kong flu - H3N2
What is the evolutionary advantage of the periodicity of flu viruses?
evasion of host-immunity
Why do flu vaccines deminish in effectivenes each year?
antigenic drift
In which situation would a flu vaccine for a given year have 0 effectivenes the following year?
antigenic shift
How does antigenic shift occur?
genetic recombination between human strains of the virus and other mammalian/avian strains (with different HA/NA families)
What is the typical amount of antigenic drift?
1% amino acid change (in antigenic portion)/year
Why did the H1N1 strain of flu reappear in 1976, after 20 years of not being observed?
likely due to a lab mishap, since it was only 1-2% different from the 1956 variety
What was the cause of 1976 swine flu scare?
Fort Dix, NJ
Military recruit from a pig farm died from flu (100% swine strain)
Why did Gerry Ford lose the election?
He made a vaccine for swine flu, even though it ended up being unnecessary...(1/1 000 000 get Guillaume-Berret syndrome = paralysis)
How did the soldier manage to catch a virus that was 100% swine?
by the inocculum effect (adult hog sneeze 500-100mL)
Which flu is the 2009 H1N1 most closely related to antigenically?
strain from the 1950s
What is the approximate size of an influenza virus?
about 100nm
What kind of nucleocapsid does influenza virus have?
helical
What is the form of the influenza genome?
ssRNA
8 pieces (segmented)
Which translated protein is not encapsidated into viral particles?
NS
What is the probability that a ssRNA virus undergoes recombination?
1/10^9
What is the possibility that influenza recombines?
50%
Which two genes in a vaccine (e.g. Flu mist) should be included from the strain you want protection against?
HA
NA
What must the other 6 genes be from?
an attenuated flu virus
What is the reservoir for Influenza A?
waterfowl
What is the total biomass of influenza A?
about the size of a baseball -- 99.9% infect waterfowl!!
What part of birds gets infected by flu?
the cloaca
Does influenza A normally cause disease in birds?
no!
Which flu caused the Stanley cup finals to be cancelled?
1918 Spanish flu (in 1919)
What was uncommon about the 1918 flu strain?
commonly killed young and healthy persons
What were some symptoms of Spanish flu?
-cyanosis (blue from lack of O2)
-hemoptysis (spitting up blood)
-ARDS (adult respiratory distress syndrome)
What was the peak in age of deaths from Spanish flu?
age 10-50
What was the main cause of mortality in younger people?
ARDS (cytokine storm)
die from immune response!
What was the main cause of death in older people?
death from secondary bacterial infection (pneumoniae)
What was a neural effect of Spanish flu?
psychiatric disorders
encephalitis lethargica (conscious paralysis)
How many people died from Spanish flu in the first 6 months?
25 million
What was the global mortality rate?
2-6%
What island suffered a loss of 22% of its population in 14 days?
Fiji
Describe the origin of the current H1N1 virus:
-3 strains: classic swine H1N1, human H3N2 and an unknown avian flu recombined
-These generated: North American H3N2, and H1N2
-These recombined with Eurasian swine flu
Where do the HA and the NA derive in the 2009 swine flu?
-H1 - classic swine flu
-N1 - Eurasian swine flu
Where did this virus really originate?
China (not Mexico)
Why has a pandemic developed?
-most people in the world do not have immunity
-good P-to-P spread
-disease-causing
Where have all the major pandemics we know of started from?
China
What is a likely reason for pandemics starting in China?
-culinary habbits
-close contact of pigs, poulty, and people
The 1957 and 1967 pandemic strains arose from recombination of flu viruses from which species?
humand and birds
Why would Peking duck be a cause of new flu pandemics?
chefs blow into cloaca
Who first tried to isolate the original 1918 flu virus?
Johan Hultin
He failed - viruses at Brevig mission were dead...
Who tried next?
Jeffrey Taubenberger
Used PCR ...succeeded
What was discovered about Spanish flu from PCR?
-It was a pure avian strain!
-Only 23 a.a. changes out of 5 672
What was different about the resurrected 1918 flu compared with recent flu strains?
-50 times as many virus particles releases from human lung cells
-32% more body is lost by mice
-3900x more virus particles in mouse (4d.)
-all mice die after 6 days (usually, none die)
What strain is Avian flu?
H5N1
When was Avian flu first detected in China?
1996
Which species of bird flu were assorted to make avian flu?
goose
quail
duck
Why was avian flu feared? Why were the date not necessary representative?
killed 6/18 infected humans
unrepresentative denominator
How was Avian flu eradicated in 1997?
by killing all the poultry
What changes in the Avian flu took place from 1997-2002?
different internal genes from duck and goose
(same H1 N5)
What was special about the avian flu of 2002?
the H5N1 flu killed wildfowl in Hong Kong!!!
What happened when this strain spread to humans?
killed 1/2 humans infected!!
What was the 2002 avian flu called?
Z genotype
How many birds have been killed to date?
240 million domesticated birds
How many humans have been infected/died?
1300 infected
150 dead
What new properties has Avian flu gained?
-capability to infect humans
-cause neurotropic damage and mortality in waterfowl
-cause death and can be transmitted in felion species
-cause neurotropic disease/death in mice
Why has Avian flu not been as severe as predicted?
cannot predent person-to-person!!
What are the requirements to produce a pandemic strain as pathogenic as Spanish flu?
1. No/little human immunity to HA proteins
2. HA - facile infection of non-respiratory tissues
3. HA - higher affinity to human sialic acid than avian sialic acid
4. Easy RNA synthesis in human cells
5. NS1 -high level of apoptosis; high inhibition of IFN induction
6. Severe pro-inflammatory effects
7. Easily infect humans
8. Significant disease in humans
9. Spread easily P-to-P
Why could a vaccination insufficient to protect against a pandemic similar to Spanish flu?
Takes about 8 months to develop a vaccine
Less than 2 months to declare a pandemic!
How does Amantidine/Rimantidine work? It is used?
-inhibits viral uncoating
-H1N1 is resistant, H3N2 frequently, H5N1 frequently
How does Tamiflu (Oseltamivir)/Zanamivir work?
-NA inhibitor
Name a virus that has dsRNA:
reovirus
Name two (-)ssRNA viruses that are segmented:
orthymyxoviruses
bunyaviruses
Name two (+)ssRNA viruses:
coronaviruses (colds)
picornaviruses (polio, rhino, flu)
Name two (-)ssRNA viruses/non-segmented:
rhabdo (rhabies)
paramixoviruses (measles, mumps)
Which type of RNA viruses can use their genome directly:
(+)ssRNA
Why type of RNA virus is independent of protein translation?
(-)ssRNA
What phases of transcription exist in (-)ssRNA?
early phase (mRNA)
late phase (ssRNA associates with NP and 3"P" protease)
What do the 8 RNAs in influenza code for?
PA1- polymerase acidic
PA2 - polymerase acidic
PB2 - polymerase basic
HA - hemagglutinin
NP - nucleocapsid protein
NA - neuraminidase
M1 -
NS1 - increase apoptosis/decrease IFN
What are three functions/effects of HA?`
1. receptor-binding (sialic acid)
2. coagulates RBCs
3. membrane fusion activity allowing viral uncoating
How HA organized?
in trimers
Why must flu replication take place in the nucleus of the host cell?
-mRNA requires splicing
-mRNA requires primers (newly synthesized host RNAs)
What are the two roles of NS1?
-increases apoptosis
-decreases interferon
Which two viral proteins are spliced?
NS
M
What does NS2 do?
function unclear
What does M2 do?
-TM protein
-ion channel protein
-low expression
-pumps H+ into viral particle to allow uncoating
What does NA do?
-digests neuraminic acid on cell surface
-receptor-destroying protein
-prevent viruses from sticking to production cell
-prevents aggregation of newly formed virions
Which two methods do viruses use to enter cells?
-direct membrane fusion (measles)
-endocytosis (flu)
Which method does flu use?
endocytosis
What pH does HA bind to sialic acid at?
7.4
What pH is required to allow uncoating?
~3.0
Which organelle allows lowering of pH?
fusion of lysosome
Why is uncoating pH dependent?
NP is bound by ionic interactions to M1
What viral protein allows H+ ions to be pumped into the virus particle so NP can be released?
M2
pH surrounding = 7.4
pH inside = 3.0
What anti-viral drug interferes with the M2 pump?
amantidine
Which areas of HA are most antigenically variable?
areas right next pocket where sialic acid fits (Fab is too small to fit)
Which antiviral is an analog of neuraminic acid and fits into NA site?
Tamiflu (Oseltamivir)