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51 Cards in this Set

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...:
-most common cause of severe diarrhea in children (type A); tends to lead to mild diarrhea or asymptomatic infection in adults (type B)
- ~55,000 annual hospitalization in US; ~600,000 deaths worldwide
-highly resistant to dehydration

symptoms
-vomiting and diarrhea for 3-8 days
-severe dehydration
-fever and abdominal pain
Rotavirus
The Rotovirus Virion:

... virus
-Triple ...
-Protects against harsh environment of the gut

Segmented, ...-stranded RNA genome

Eleven segments encode for 6 structural and 5 nonstructural proteins
Capsid
capsid
double
Rotovirus Replicative Viral Cycle:

Occurs in the ...

Activation of ... on the outer capsid occurs in the gut

Virus supplies all the enzymes necessary to replicate the dsRNA

Replication and production of mRNA transcripts take place within the double ...
cytoplasm
VP4
capsid
Important points regarding attachment and penetration, macromolecule synthesis and assembly:

outer shell has two important proteins: V4 and V7
-... serves as the attachment protein
-... must be cleaved before it can act as a fusion protein

exact means of entry not determined, potentially by receptor-mediated ... AND/OR fusion event

the replication and transcription of the dsRNA occurs within the ... or inner capsid
-rotavirus carry all the machinery necessary within the ...
-occurs in a manner similar to the (...) RNA viruses
-the viral mRNA and replicated (...) RNA strands are produced from the (-) RNA strand
-mRNAs are both ... and polyadenylated
-the mRNAs and (+) RNA strands exits from the inner capsid into the cytoplasm

translation and assembly
-in the cytoplasm, the mRNA are translated into both the structural and non-structural proteins which are assembled around the (...) strand RNA -once the capsids have been assembled, the (...) strand RNA is copied and the double stranded genome is complete once again
V7
V4
endocytosis
core
capsid
-
+
capped
+
+
Rotavirus Viral Spread:

spread from person-to-person by the ... route or by contaminated water
-both symptomatic and asymptomatic individuals shed the virus in feces

potentially spread by respiratory route

contained within gastrointestinal tract
-intestinal digestive enzymes are required for cleavage of outer capsid proteins
-cleavage required for cellular ...

cytolytic action on the intestinal epithelium leads to ... loss and prevents readsorption of water
fecal-oral
entry
electrolyte
Evasion of Host Defenses by the Rotavirus:

dsRNA is maintained within the ...
-results in little to no ... production, as dsRNA is never ‘seen’ by the host cell

no ... protective immunity
-infected cells will incite an innate response and eventually an adaptive response
-by the time the adaptive immune response is turned on, a majority of virus is swept away in the feces
-remaining virus is usually contained by the innate response while the neutralizing antibodies simply clean up the mess
-infection usually generates incomplete protective immunity against subsequent infections

antigenic ...
-results in multiple serotypes that circulate in the population
double capsid
interferon
long term
drift
Viral Pathogenesis of Rotavirus:

-Major cause of severe inflammation of the intestine (...)
-Rotavirus normally infects only a small fraction of the villus cells of the digestive tract
-Frequent symptoms include vomiting, diarrhea and fever
-Vomiting, diarrhea and fever are caused through the action of the ... system
gastroenteritis
nervous
Viral Pathogenesis of Rotavirus

...
-defense designed to clear the upper gastrointestinal tract
-inflammation sensed by the nerves innervating the gastrointestinal tract
*signal transmitted to the medulla

...
-second defense mechanism used to clear rotavirus from the gastrointestinal tract
-viral infection stimulates the enteric nervous system of the small intestine
*signals stimulate the crypt cells of the intestinal villi resulting the secretion of water into the lumen

...
-inflammatory cytokines stimulate nerves in the intestine that signal sent to the fever center of the brain
Vomiting
Diarrhea
Fever
The Adenovirus Virion:

... viruses
-Icosehedral
-Viral ... proteins project from vertices

Genome is linear, ...-stranded DNA

Genome encodes for >30 proteins
Capsid
attachment
double
Adenovirus:

family of viruses with ~50 different serotypes
-serotypes have different ... (cell-specificities) and result in different disease states
-cause acute and chronic infection
*... infections may result in latency or transformation

most of the serotypes cause ... infections

serotypes ... and ... are enteric adenoviruses and cause gastroenteritis
tropisms
chronic
respiratory tract
40 and 41
...:

-account for around 15% of gastroenteritis cases
-symptoms include vomiting, diarrhea and fever
Enteric adenoviruses
Adenovirus Replicative Viral Cycle:

... infection

entire replicative viral cycle takes ~2 days

similar to ... replicative cycle,
Two exceptions:
-the synthesis of the macromolecules, genome is ...-stranded DNA
-the viral particles are released by ... processes, not ...
cytolytic
influenza
double
lytic
budding
Entry of Adenovirus:

-enter the cell via receptor-mediated ...
-partial breakdown of the ... followed by delivery of the double-stranded DNA genome to the ...
endocytosis
nucleocapsid
nucleus
Novel DNA replication strategy:

the replication cycle of the adenovirus must be ... from the cell’s replication cycle
-remember, cellular DNA replication occurs only ... during its cell cycle
-the production of one viral particle per cell cycle would be a disadvantage

any resting cells that are infected must be turned on
-immediately after infection, the ... proteins turn on the DNA replication cycle (G0 to G1 phase of the cell cycle)
-allows for the amassing of materials (enzymes, dNTPs, etc) necessary for replication
-the cellular DNA synthesis is subsequently turned ... allowing for preferential replication and transcription of the viral genome

selective transport and translation of viral mRNA observed
uncoupled
once
E1A
off
Enteric Adenovirus Spread:

Spread by ... route

Containment of the enteric adenovirus to the gastrointestinal tract due to lack of adenovirus receptors on ... cells
-Observe infection of the mucoepithelial cells of the gastrointestinal tract
-No active infection of ... cells
fecal-oral
dendritic
dendritic
Evasion of Host Defenses by the Adenovirus:

-the ... cycle of adenovirus take a considerable amount of time (~2 days)
-countermeasures ensure that the viral replicative cycle is completed before the ... of the infected cells
replicative
destruction
Delay apoptosis of the infected cell:

-a viral protein (E1B-55K) blocks transcription of the cellular genes that activate the ... pathway
-another viral protein (E1B-19K) binds and inactivates the host proteins involved in ... apoptosis
-late in the infection, a third protein called the ... protein will cause the cell to burst and viral particles to be released
apoptotic
initiating
adenovirus death
Reduction of interferon production through the use of decoy RNA molecules:

-concurrent transcription from both DNA strands allows for the formation of ...
-to protect itself from the interferon the infection induces, the cell produces ... viral RNA molecules (VA RNA)
-the VA RNAs actively binds the ... and inactivates it
dsRNA
decoy
PRK
Interference of MHC class I antigen presentation:

-a viral protein (E3-19K) sets up residence in the endoplasmic reticulum
-the protein is able to attach to and prevent the ... molecules from being presented on the cell surface
-... do not know there is an active infection
MHC class I
CTL
Removal of Fas from the surface of adenovirus infected cells:

-a viral protein (RID) attaches to Fas found on the cell surface of adenovirus infected cells and ... them
-another viral protein (E3-14.7K) blocks the ... through the Fas
-neutralizes the ability of both CTLs and natural killer cells to destroy the infected cells
removes
signaling
Adenovirus:

-different serotypes cause upper respiratory infections, childhood pneumonia, conjunctivitis and gastroenteritis
-some serotypes can infect both the respiratory tract and the gastrointestinal tract (serotype ... and ...)
4 and 7
Enteric adenoviruses, serotypes ... and ...:

second to rotavirus, are a frequent cause of infantile diarrhea

most children have been infected by an enteric adenovirus by the time they are 3-4 years old

adenovirus spread by the same route as ..., infect and kill the same cells and are not disseminated throughout the body

rotaviruses and enteric adenoviruses have very different time courses
-symptoms of an enteric adenovirus infection appear ... than seen in rotavirus infection
-symptoms last ... than a rotavirus infection
40 and 41
rotaviruses
later
longer
The Hepatitis A Virion:

... capsid
-Icosehedral

Genome is ...-stranded, (...) RNA

Environmentally stable
-Resistant to ... conditions
Naked
single
(+)
acidic
Hepatitis A (also called infectious hepatitis):

... disease caused by the hepatitis A virus

symptoms include:
-jaundice, fatigue, abdominal pain, loss of appetite, nausea, diarrhea and fever
- usually the result of immune-mediated damage to the ...
liver
liver
Hepatitis A Replicative Viral Cycle:

-Replicative viral cycle is similar to the ... cycle
-Major difference between hepatitis A and rhinovirus replication is that a hepatitis A infection does not ... the cells; ...
rhinovirus
kill
noncytolytic
Hepatitis A Viral Spread:

-... infection
-unable to establish a chronic infection as it is quickly eliminated by the ... response
-briefly appears in the ...
acute
immune
blood
Person-to-person Hepatitis A Viral Spread:

transmitted by ... route

ingestion of contaminated food and water

shellfish from sewage-contaminated water

commonly transmitted by children, food handlers and daycare workers
-will see transmission via ... between IV drugs users and sexual contact with infected individuals
fecal-oral
blood
Within host, targeting the liver:

ingestion of hepatitis A leads to entry into the ... via the oropharynx or the epithelium lining of the intestine

from the bloodstream, hepatitis A virus will enter the ...
-blood continually circulates through the liver

in the liver, the hepatitis A virus will replicate in ... and ... cells

the new propagated viruses are released into the ... and are subsequently emptied into the intestine
-released into the stool
bloodstream
liver
hepatocytes
Kupffer’s
bile ducts
Viral clearance of Hepatitis A:

... limits viral replication
-CTLs and natural killer cells eliminate the infected cells

antibodies, complement and antibody-dependent cellular cytotoxicity also facilitate clearance
-know to induce immunopathology (icterus symptoms: jaundice, dark urine )
interferon
Evasion of Host Defenses by the Hepatitis A Virus:

Temporarily avoids destruction and clearance by the immune system by detouring through the ...
-Hepatitis A-specific IgA in the intestines does not mediate ... of the virus
-Instead hepatitis A-specific IgA bound to hepatitis enters the bloodstream and is ... to the liver
-Hepatocytes and Kupffer’s cells take up the IgA:hepatitis A complexes where an infection will be initiated
liver
phagocytosis
transported
Evasion of Host Defenses by the Hepatitis A Virus:

-hepatitis A takes a detour to the ... avoiding the immune responses generated in the intestine
liver
Summary of the evasion process:

hepatitis A infects the ... layer of the intestine
-some of the virus is taken up by ... cells and is transported to surrounding lymphoid tissues where ... cells are activated to produce hepatitis A-specific antibodies (IgA)

the plasma cells producing hepatitis A-specific IgA antibodies take up residence in the intestinal tissue

the IgA binds to the hepatitis A virus, but is unable to induce their destruction and clearance by phagocytes
-phagocytes lack the ... receptors for IgA

the IgA:hepatitis A virus complex is instead collected by the ... and poured into the bloodstream

the liver cells have Fc receptors for the IgA and will take up the complexes
-once inside the cells, hepatitis A avoids destruction and set up an infection
-within the liver, the entire ... immune response must be re-initiated
epithelial
M
B
Fc
lymphatics
adaptive
Hepatitis B virion:

...
-Contains the hepatitis B surface antigen (HBsAG)

Genome is a ..., partially ...-stranded DNA
-Associated with a protein kinase and polymerase

Also called the Dane particle
Envelope
circular
double
Hepatitis B (also called serum hepatitis):

... disease caused by the hepatitis B virus

symptoms include jaundice, fatigue, abdominal pain, loss of appetite, nausea, vomiting and joint pain
-caused by cell-mediated immunity and immune complexes
-30% of infected individuals are ...
-adults often display ... symptoms than children
liver
asymptomatic
more
Hepatitis B Replicative Cycle:

-Replication strategy uses ... activity (replicates through an RNA intermediate)
-generation of many empty particles (releases antigenic decoy particles)
-non-...
reverse transcriptase
cytolytic
Cycle (Hepatitis B)
Events between attachment and uncoating not well understood:

-attachment mediated by HBsAG leading to ...
fusion
Intermediate RNA produced during macromolecule synthesis (Hepatitis B):

relaxed circular genome is converted to ... closed circular DNA

the host cell RNA polymerase is responsible for:
1. Transcribing the ... strand of the DNA into mRNA to produce the proteins necessary for viral replication
2. Produces a full-length complementary strand of ‘genomic’ RNA

the viral reverse transcriptase is responsible for:
1. Production of a complementary DNA strand (...) from the ‘genomic’ RNA; this occurs as the viral ... is being assembled around the genome
2. Subsequent production of a complementary DNA strand (...) from the (...) DNA strand; interrupted by the completion of the viral capsid resulting in a ... double stranded DNA molecule
covalently
negative
-
capsid
+
-
partial
Hepatitis B Viral Spread:

spread efficiently by blood-to-blood contact
-most common natural route is during ... (vertical transmission); blood and vaginal secretions of an infected mother is passed to the blood of her child during childbirth
*20% of children born to a hepatitis B infected mother will become infected

other routes of transmission include unprotected sex between an infected and uninfected individual and through the sharing of contaminated ... used for injection of drugs
birth
needles
Hepatitis B Viral Spread within an individual:

initial infection occurs in blood that will circulate through the ... (the target of hepatitis B)
-step potentially halted by ... antibodies

within the liver, a mass infection leads to the high levels of virus production that will enter the bloodstream (...)
-step potentially halted by cell-mediated immunity

viremia leads to the presence of hepatitis B in not only the blood, but also mother’s milk, vaginal secretions/semen, and saliva
-begins ... cycle again
liver
neutralizing
viremia
transmission
Evasion of Host Defenses by the Hepatitis B Virus:

Non-cytolytic and no activation of cells to produce ...
-Hepatitis B infection does not lead to cell ...
-No formation of ...

Production of decoy viruses
-The replicative viral cycle of hepatitis B results in many empty “...” viral particles
-The decoys deplete the ... antibodies specific for the HBsAg
interferon
death
dsRNA
decoy
neutralizing
Viral Pathogenesis of Hepatitis B:

hepatitis B virus leads to acute or chronic, symptomatic or asymptomatic disease
-clinical presentation is more severe in adults than children, infection may be ...

infection is characterized by long incubation periods and insidious onset
-prodromal period that includes fever, malaise and anorexia followed by nausea, vomiting, abdominal discomfort and chills -classic ... symptoms (jaundice, dark urine and pale stools) of liver damage follow prodromal symptoms
asymptomatic
icteric
... infection of Hepatitis B:

-viral infection of the liver that does not directly cause cytopathology
-cell-mediated immune lysis of cells produces the symptoms and resolves the infection
Acute
... infection of Hepatitis B:

limited cell-mediated immune response leads to chronic disease

associated with mild disease or individual may even by asymptomatic

chronically infected individuals are the major source for the spread of hepatitis ...

individuals with chronic active hepatitis B experience continual destruction of the ...
-scarring of the liver, cirrhosis, liver failure and primary hepatocellular carcinoma
-co-infection with the delta agent (hepatitis D virus) leads to fulminant hepatitis
Chronic
A
liver
HTVL-1 Virion:

Human T-leukemia virus or
human T cell lymphotropic virus

...
-Surrounds an icosahedral capsid

Genome is composed of identical copies of ...-stranded, ... RNA

Contains reverse transcriptase and integrase
Envelope
single
positive
HTLV-1:

first ... discovered

associated with adult T-cell leukemia/lymphoma (ATLL)

also associated with HTLV-1 associated myelopathy/Tropical spastic pararparesis (HAM-TSP)
-characterized by sensory and ... deficits, incontinence and impotence
retrovirus
motor
HTLV-1 Replicative Cycle:

Very similar to the replicative cycle of ...

Differences
-The viral attachment proteins bind to an ... receptor
-HTLV-1 prefers to remain in a ... state, producing very few new viral particles
HIV-1
undefined
latent
HTLV-1 Viral Spread:

virus has low ...

by establishing ..., the HTLV-1 makes up for its low infectivity
-infected individuals becomes carriers for life
infectivity
latency
HTLV-1 Transmission:

commonly passed from mother to child by the transfer of virus-infected cells through the mother’s ...
-also passed by blood, sexual contact and shared needles

the transferred infected cells subsequently produce infectious viral particles that infect ... cells of the recipient
OR
infected CD4+ T cells from the infected individual fuse with the ... CD4+ T cells of the recipient
breast milk
CD4+ T
uninfected
HTLV-1 Spread within host:

primarily infect ... cells

provirus integrates into the cellular genome of a high number of CD4+ cells
-initially mediated by a transcription factor called ... which causes the infected cell to proliferate; generate a large population of cells that contain HTLV-1 without having to generate infectious virus
-spread can occur when an infected cell fuses with an uninfected cell (formation of ...)
-infectious viral particles can infect other ... cells
CD4+ T
Tax
syncytia
CD4+ T
HTLV-1 Pathogenesis

95% of HTLV-1 infections never result in ...

chronic infection

initial infections with HTLV-1 uniformly ...
-non-cytolytic
-establishment of latency in a majority of infected cells

2% of HTLV-1 infected individuals are at increased risk for developing adult T-cell leukemia and lymphoma (ATLL)
-2% of HTLV-1 infected individuals are at increased risk for developing neurological disease
-HTLV-1 associated myelopathy/tropical spastic pararparesis (HAM-TSP)
-motor neurons of the spinal cord become ...
-characterized by sensory and motor deficits, incontinence and impotence
-both ATLL and HAM-TSP develop 30-50 years after original infection
disease
asymptomatic
demyelinated
Evasion of Host Defenses by the HTLV-1:

Establishment of ...
-Integrated provirus is passed down to daughter cells when infected cells proliferate
-Provirus is copied by the cell’s high-fidelity DNA polymerase

... infected cells cannot be distinguished from uninfected cells
latency
Latently