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42 Cards in this Set

  • Front
  • Back
Influenza is classified as what type of virus
orthomyxovirus
Major sx of influenza infection
resp disease w/ fever and myalgia
Mostclinically significant serotype of influenza
Influenza A (cause epidemics and infect same host more than once in lifetime)
Describe the ultrastructure of the Influenza A virus
-enveloped

-very polymorphic particles

-different shapes (spherical and others filamentous)

-contain glycoprotein spike projections

-helical Ribonucleoprotein assemblage
Describe the genome of the influenza A virus
-RNA
-segmented
-minus-strand (need to be made to mRNA first)
What proteins form the projecting spikes on the influenza envelope
hemagluttin (HA)

and

neuraminidase (NA)
Describe the oles of M1, M2, and Nucleoprotein (NP) for the flu virus
-M1: under envelope and associates with NP

-NP: coats the RNA segment

-M2: tetrameric membrane spanning complex
What is the roles of PB1, PB2, and PA enzymes for the flu virus?
present in virion, bound to helical ribonucleoproteins

participate in viral RNA replication
What does HA bind to on cell surfaces?
sialic acid
Describe the synthesis of HA in virus infected cells
cotranslational insertion into ER

protein folding and oligomerization

3 units are made (for a trimer)

each monomeric unit is proteolytically cleaved (generates amino terminal and membrane anchored fragments)
General roles of HA and NA in influenza infection
HA: promote virus binding

NA: promote virus release and dissemination
Describe general shape of NA
four identical molecules form a box-shaped tetramer

box tetramer attaches to particle membrane by a slender stalk

outer surface of NA tetramer recognizes sialic acid and cleaves it
Initial step in influenza infection
HA attachment to sialic acid receptors

multiple trimers (up to 500) involved

entire particles are internalized into endosome
Describe endosome acidification, and how this plays a role in influenza infection
endosome pH is low (5-6)

acid environment alters flu particle in 2 ways:

1. protons bleed thorugh M2 pores = acidify virion interior. This frees ribonucleoprotein complexes and gets them ready for transport into the nucleus

2. alters charge of HA spike, changes their shape, and promotes fusion between flu and endosome membranes.

End result = delivery of nucleocapsids into cell cytosol
Where are nucleocaspids targeted to in influenza infection? What is the goal of this?
nucleus

for transcription to occur
What to PB2, PB1, and PA form at the cell nucleus?
RNA transcriptase
What is "cap-snatching"?
virulent form of parasitism, involved in flu transcription

virus-encoded endonuclease cleaves 5' terminal 10-13 nucldotides from host transcript

short RNAs used to prime viral transcription

End result: promotes VIRAl transcription (and thus translation), but disables cellular protein synthesis
How do the newly synthesized HA, NA, and M2 get to the infected cell surface? where are the rest of the proteins targeted to?
utilize the normal cellular exocytic pathway

rest- go back to the nucleus
Describe the replication of the virion genome
late in infection

virion RNAs of flu serve as templates for synthesis of cRNA (templates for minus strand virion RNAs)
Describe packaging process of RNA virions during infection. Which proteins are involved?
RNAs are packaged in conjunction with NP, transcriptase proteins, and M1.

Core migrates toward cell surface, acquire envelope, and later HA, NA, and M2. = BUDDING
BIG THREE important things regarding influenza epidemiology
1. Influenza A infection prevented by antibody to HA protein. Lots of HA proteins however, so antibodies form prior infection is not always useful (in cases of novel influenza)

2. Broad range of hosts for influenza provides transmission from animals to humans

3. 2 flu viruses can infect the same cell, and RNA segments from parent viruses can reassert = novel gene constellations in progeny.
Mechanism responsible for influenza pandemics
antigenic shift

flu antigen (HA) in one strain is shifted to a type not previously observed in human populations. shift is from reassotment of RNA segments = pathogenic assortment.
Mechanism responsible for influenza epidemics
occur more frequently vs pandemics

results from ANTIGENIC DRIFT.

Flu antigen (HA) drifts to a marginally altered form (due to inherently error prone flu replication) = escape immune surveilance
Mechanism responsible for influenza endemics
infection of individuals who escaped infection during previous epidemics
Major sx of influenza infection
fever

sore throat

nonproductive cough

ha
where does the influenza virus replicate?
ciliated columnar epithelium of resp tract
describe major risk with influenza infection
secondary pneumonia from bacterial infection (s. aureus) can occur
Describe age group/risk factors for most influenza related deaths
>65+ yo

risk increased in those suffering from chronic pulm or cardiac diseases
Lab diagnosis of influenza is made how?
throat swabs by virus cultivation in cell lines


viral antigen identification in infected cells by EIA

SEROLOGY NOT HELPFUL (PRIOR ANTIBODIES CONFUSING)
Major classifications of influenza
1. Serotypes (A,B,C)

2. Host of origin

3. geographic location of isolate

4. strain number, yr of isolation

5. HA and NA subtypes
What is the critical immunogen for influenza vaccines?
HA
How are influenza vaccines made?
virus is grown in embryonated chicken egg

purified and inactivated with formalin

usually standarized for immunoreactive HA
Describe the concept of the live attenuated influenza vaccination
administered via nasal spray

virus vaccine replicates enough to elicit powerful immune response

does not replicate enough to cause disease
How does Amantadine work?
antiviral against influanza A

blocks M2 protein ==> stops flow of protons into virion interior during penetration

nucleocapsids are incompetent for migration due to this
How to oseltamivir and zanamizir work?
block activity of NA, and limit dissemination of infection in resp tract

block influenza A and B
What type of virus is the rhinovirus?
picornavirus
Describe major sx and optimal conditions for the rhinovirus
acute upper resp disease

particles = acid labile (no enteric infection), and growth os optimal in low temps found in nasopharynx
When do rhinovirus epidemics peak? incubation and sx duration?
spring and fall peaks

incubation 2-3 days

sx for 3-7 days
illnesses associated with adenovirus
upper resp disease

conjunctivitis/pink eye
Adenovirus is what type of virus?
non-enveloped

DNa virus

lots of serotypic diversity
population most frequently infectd with adenovirus?

major spread routes?

epidemic periods?
infants

resp or fecal-oral

late winter = epidemic time
Is there a vaccine for addenovirus?
live attenuated vaccine against serotypes 4 and 7

only given to military recruits