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38 Cards in this Set

  • Front
  • Back
General Information Regarding Influenza and the Influenza Virus:

Influenza is a contagious ... agent caused by the influenza virus

Influenza varies in severity, potentially fatal due to complications associated with the ... (i.e. pneumonia and bronchitis)

Produces “Flu-like symptoms”
respiratory
flu
Types of influenza virus:

three types: A, B and C
-types ... and ... account for seasonal epidemics; type ... infections tend to be mild

type A viruses divided into subtypes based on the hemagglutinin (H) and neuramidase (N) proteins
-# hemagglutinin subtypes and # neuramidase subtypes
-subtypes can be broken down into different strains

type ... viruses are not divided into subtypes
A and B
C
16
9
B
Influenza vaccine:

each annual influenza vaccine contains strains of influenza (the current subtypes) A (...), A (...) and influenza B
H1N1
H3N2
The influenza virion:

virion consists of a ... within a lipid envelope
-the nucleocapsid consists of a ...-stranded, ... RNA genome and associated RNA-dependent polymerases
*the genome exists in 8 segments (each segment encoding for either a structural or non-structural protein)

the envelope has two prominent glycoproteins called ... (which is necessary for binding) and ...

highly ... (different shapes)
nucleocapsid
single
negative
hemagglutinin (H)
neuramidase (N)
pleomorphic
Influenza Virus Replication:

establishes an ... infection
acute
Influenza Virus Replication:

1. And 2. Recognition and Attachment
-the viral glycoprotein ... recognizes and attaches to ... residues found on receptors on the host cells

3. Penetration
-receptor-mediated ...

4. Uncoating
-decrease in pH of the endosome leads to changes in the virus’s coats allowing for fusion of the viral ... to the endosome
-fusion always for the ... of the viral genome
hemagglutinin
sialic acid
endocytosis
envelope
release
Influenza Virus Replication (cont.):

5. Macromolecular synthesis
-the influenza genome is replicated and transcribed in the ... while translation of viral proteins occurs in the ...
-(...) strand RNA must be converted to (...) strand RNA by the RNA polymerase supplied by the influenza virus
*(...) strand (or mRNA) provides for multiple copies of the (...) RNA genome to be produced and the for the translation of viral mRNA into proteins
-during the production of the mRNAs, viral proteins cleave the 5’ cap off of the ... mRNA and transfer the cap to the ... mRNA
*shifts protein synthesis from the cellular mRNA to the viral mRNA- NO ... protein synthesis
*cell is taken over by the influenza virus, high numbers of viral proteins and particles overcrowd the cell, leading to its ...

6. Assembly of virus
-occurs at the cell ... at regions of highly concentrated HA and NA proteins

7. Budding of enveloped viruses
-assembly and budding is associated with the plasma membrane
-as the influenza virions pick up cellular receptors that contain ... molecules on the cell surface
*... works to cleave off the sialic acid molecules
nucleus
cytoplasm
-
+
+
-
cellular
viral
cellular
death
membrane
sialic acid
neuramidase
Influenza Viral Spread:

Likes warm, dark places

Typically contained within the ... respiratory tract (likes being in ...)

establishes an acute infection

spread person-to-person by virus-contaminated ... secretions
lower
lungs
respiratory
Routes of infection (influenza):

... (primary way)
droplets, containing the virus, are expelled into the environment by coughing or sneezing and inhaled by another individual
-coughing and sneezing are the natural consequence of epithelial cell death
*viral infection
*immune response
infects epithelial cells of the upper and lower respiratory tracts
-presence of ... on all epithelial cells

... (secondary way)
the influenza virus can survive for several days on non-porous surfaces
-contact with the mucosa can lead to infection
Inhalation
sialic acids
Fomites
Evasion of Host Defenses by the Influenza Virus

Overriding the effects of interferon
Normal action of inteferons
-interferons are produced by ... infected cells in response to the presence of dsRNA
*IFN-α and IFN-β have three major functions:
1. Resistance to viral ...
2. Increase in ... expression (warns neighboring cells)
3. Activate ... cells
-interferons warn neighboring cells of the viral infection
*this warning increases the production of a protein kinase called ... in neighboring cells
-when the virus spreads and infects neighboring cells, the PKR senses the dsRNA and subsequently phosphorylates and inactivates ... which is required for protein synthesis
*loss of protein synthesis leads to the death of the virally infect cell

The counteraction
-the viral genome encodes an early gene product called ...
-... binds dsRNA, effectively competing with the PKR produced by the cell (overcomes interferon)
-the influenza virus needs only enough time to complete its viral replication cycle
virally
replication
MHC class I
NK
PKR
eIF2
NS1
NS1
Evasion of Host Defenses by the Influenza Virus

Antigenic ...
process by which point mutations in influenza virus genes cause differences in the structure of the viral surface antigen
-result of the low fidelity of the RNA polymerase
-allows for new neutralizing antibodies

accounts for the year to year antigenic differences in strains of influenza virus
-may have a slight change in disease severity and some deaths
drift
Antigenic ...

process by which the influenza viruses reassort or exchange their segmented genomes and change their surface antigens radically
-development of new types of influenza viruses

results in new viruses that lead to influenza pandemics
-infection of a high proportion of population
-more severe disease and greater number of deaths
Shift
Reservoirs of influenza virus

type ... infects humans and many others animal species (zoonose)
-including horses, pigs and birds

type ... and ... predominantly infect humans
A
B and C
How new pandemics strains arise-one theory:

recombinant viruses arise in pigs that have been co-infected with avian and human strains of influenza

the genomes of both viruses are ... and result in new strains

the new strains are potentially transmitted back to human (and birds)
-humans with no protective immunity against the new strain will be aggressively infected
reassorted
Antigenic shift:

Only occurs in type ...

... event unlike antigenic drift

Tend to result in influenza pandemics
A
Infrequent
Viral pathogenesis of influenza virus:

inhalation of the virus is followed by the establishment of ... in the upper and lower respiratory infections
-induction of ... production
*... is responsible for the fever, muscle aches, headaches and fatigue
-infection targets and damages mucus-secreting, ciliated and other epithelial cells destroying the ... barriers
*damage mobilizes the ... immune response
*cellular damage accounts for the sore throat, cough and hoarseness

the destruction of the epithelial and mucosal level an individual susceptible to complications -infection with superinfecting bacteria leads to influenza-associated ...
-inflammation in lower respiratory tract decreases oxygen exchange, narrows airways and lower pulmonary function exacerbating pre-exiting diseases such as asthma and ...
infection
interferon
interferon
physical
adaptive
pneumonia
cystic fibrosis
Rhinovirus:

Capsid
-Environmentally ...

Genome is a ...-stranded (...) RNA molecule

There are over 100 different ...
stable
single
+
serotypes
The common cold, the primary illness of the rhinovirus:

infection established primarily in the ... respiratory tract, but also shown to replicate in the ... respiratory tract

establishes an acute infection
upper
lower
Symptoms of rhinovirus infection:

the ..., accounts for 50% of cases
-predominant symptoms include sneezing, nasal obstruction, nasal discharge and sore throat
-other symptoms include headache cough and malaise (fever is low-grade or...)

1/3 of individuals infected with rhinovirus will be ...

complications include precipitant of asthma and exacerbation of chronic bronchitis and cystic fibrosis
common cold
absent
asymptomatic
Viral replication of rhinovirus:

Features:
-occurs in the ...
-Cap-... translation of viral mRNA
-Shuts down cellular cap-dependent translation
-Cytolytic
cytoplasm
independent
Viral replication of rhinovirus:

1. Recognition

2. Attachment
majority of rhinovirus serotypes bind to ...
-expressed on epithelial cells

3. Penetration

4. Uncoating

5. Macromolecular synthesis
the influenza genome is replicated and transcribed in the ..., translation of viral proteins occurs in the ...

Translation
-internal ribosome entry site (IRES) directs translation of mRNA by internal ribosome binding
-rhinovirus encodes a protein that disrupts cap-dependent initiation, shutting down translation of capped, cellular mRNAs

Genome replication
-upon entry of the single-stranded (...) RNA in the cytoplasm it is translated
*proteins necessary for genome replication and production of new viral particles
-first step copy (...) strand to form (...) strand intermediate, followed by the production of many (...) strand genomes
-replication occurs on small membranous vesicles that are induced by viral proteins

6. Assembly of virus
-occurs in the ...
-occurs when large pool of capsid proteins is amassed

7. Release of virus
-are released ... from cell
ICAM-1
nucleus
cytoplasm
+
+
-
+
cytoplasm
lytically
Viral Spread of Rhinovirus:

Spread from one host to another by virus contaminated ... secretions

Establishes an acute infection

Contained within the ... respiratory tract

Higher infectivity in tissues that maintain a temperature around 91°F
-Nares and upper respiratory tract

... prefers normal physiological temperatures
-Lower respiratory tract
respiratory
upper
Influenza
Viral Spread of Rhinovirus:

Spread of infection mediated by ...:

ensures efficient transmission to a new host

spreads infection to the Eustachian tubes and the sinuses
-otitis media and sinusitis


Special note: rhinovirus has been isolated from the lower respiratory tract
sneezing
Evasion of Host Defenses by the Rhinovirus:

Decreased ... of interferon (in direct contrast with influenza):
-interferes with the ... of interferon by disrupting its transport out of virally-infected cells

Rapid clearance by the ... immune response “attack and surrender” (in direct contrast with influenza)
-immune defense against rhinovirus is primarily mediated by the ... immune response
*neutralizing antibodies are not made in sufficient quantities to protect against subsequent attacks

Antigenic ... (new epitope situations)
-error-prone RNA polymerase
-generation of hundreds of different strains
*the different strains are not efficiently keep in check by neutralizing antibodies
production
production
innate
innate
drift
Viral pathogenesis of Rhinovirus:

Infection most efficiently established in the ... respiratory tract

Associated symptoms are due mainly to upper respiratory tract inflammation caused by the strong ... immunity response
upper
innate
Viral Pathogenesis of Rhinovirus:

Cause of symptoms:

Sneeze
-triggered by the inflammation resulting from the ... response

Runny nose
-inflammatory mediators cause increased permeability of the capillaries that line the tissues of the upper respiratory tract

Congestion
-fluid accumulation due to the increased capillary permeability
*some of the fluid is trapped and causes tissues to swell, constricting the airways
innate
Impact of cytokines:

Lower ... production:
-milder “flu-like symptoms

...
-released by macrophage responding to the rhinovirus
*triggers a low grade fever
*controls the spread of the infection by effectively ... the body temperature
interferon
IL-1
increasing
Measles (Rubeola) and the Measles Virus:

Enveloped

Genome is a ...-stranded (...) RNA molecule

Only ... serotype exists

Structurally similar to ... virus
single
-
one
influenza
Measles (Rubeola) :

febrile illness

incubation period of 7-10 days
-prodrome characterized by high fever, cough, coryza (runny nose), conjunctivitis (red eye) and photophobia
-individual is most ... during this period

appearance of ... (major signal for measles) after disease symptoms begin
-within 24 hours there is the appearance of an extensive maculopapular rash that will cover the entire body

serious complications include pneumonia, encephalitis and corneal scarring
contagious
Koplik’s spots
Viral Replication of Measles Virus:

-similar replication process as the ... virus, with one exception
-entry strategies similar to that of the ...
-Macromolecular synthesis occurs in ...
-Cytolytic
influenza
rhinovirus
cytoplasm
Viral replication of measles virus:

1. Recognition

2. Attachment
-recognition and binding to the cell receptor, the glycoprotein ..., is mediated by the hemagglutinin protein

3. Penetration
-after binding to the cellular receptor, the envelope fuses with the cell membrane releasing the (...) RNA into the cytoplasm
-fuses to cell membrane through the ... protein

4. Uncoating

5. Macromolecular synthesis
-genome replication and translation of viral proteins occurs in the ...
-(...) RNA converted to (...) RNA by the RNA-dependent RNA polymerase for replication of the genome
* the RNA polymerase is able to replicate many full length (...) RNA genome from the (...) mRNA
-the RNA polymerase is also capable of transcribing (+) mRNAs from the (-) RNA strands

6. Assembly of virus

7. Budding of enveloped viruses
-assembly and budding is associated with the plasma membrane

8.Release of virus
CD150
-
fusion
cytoplasm
-
+
-
+
Viral Spread of Measles:

-transmitted person to person by ... secretions
respiratory
Mechanism of viral spread (measles):

infection contracted by inhalation of respiratory secretions from an infected individual

initial infection established in the epithelial cells of the respiratory tract
-controlled by the ... immune response

... cells carry the virus to the lymph nodes where it gains access to the lymphatics establishing a systemic infection and ...

the wide spread dissemination of the virus leads to infection of the conjunctive, respiratory tract, urinary tract, small blood vessels, lymphatic system and the central nervous system

appearance of characteristic maculopapular rash as the result of T cells releasing ...

... typically follows rash
innate
dendritic
viremia
cytokines
recovery
Viral pathogenesis of measles virus:

establishment of a ... infection

immune response causes ...
-inflamed mucosal surfaces-conjunctivitis
-demyelination-encephalomyelitis

immunosuppression leaving an infected individual susceptible to secondary infection
-Pneumonia
systemic
inflammation
Evasion of Host Defenses by the Measles Virus:

One serotype of measles virus exists:

-mutations are introduced into the viral genome by the RNA polymerase
-mutated viral coat proteins lead to the loss of viral function (non-infectious) and are no longer recognized by ... antibodies
-resulted in the existence of one serotype of measles virus
neutralizing
Evasion of Host Defenses by the Measles Virus:

Spread of measles virus from cell to cell through ... formation:

-the fusion protein on the measles virus facilitates the fusion of the infected cell with uninfected cells leading to the formation of ... (giant, multinucleated cell)
-measles virus avoids being detected by the neutralizing antibodies
-CTLs are primarily responsible for destroying the ...
syncytia
syncytia
syncytia
Evasion of Host Defenses by the Measles Virus:

... of interferon production:

-mechanism unknown
Repression
Evasion of Host Defenses by the Measles Virus:

... immune response:

stems from the infection and destruction of dendritic cells and macrophage
-dendritic cells and macrophages are directly involved in the activation of the ... immune response

infected ... cells may trigger T cells to undergo apoptosis
Suppresses
adaptive
dendritic