IAH Flashcards
(207 cards)
1
Q
What is the plaque forming assay?
A
tissue culture assay for quantifying infectious virus
2
Q
What is a focus assay?
A
Counting the areas where cells overgrow
3
Q
What are the components of virion particle?
A
genome, enzmes, auxialry protein, structural proteins, attachment proteins, fusion proteins, membrane
4
Q
What is the physiology of picornavirus?
A
icosahedral, ssRNA+, no lipid envelope, no tegmentum, pH stability: enterovirus ph3-9
rhino virus only ph6+
5
Q
Polio infection vs. disease?
A
most were innapparent (asymptomatic)
mild illness-minor febrile illness
only 0.1-2% resulted in paralytic poliomyeltitis:
complication paralysis
6
Q
How was picornavirus diagnosed?
A
serologic, PCR, virus isolation from CSF, stool specimens and throat washing
7
Q
Polio had three major epidemiological phases?
A
endemic
virus encountered at early age, high rate of sublinical infections, encounter at maternal antibodies
epidemic
late 1800s, encounter virus at later age, bc of hygeine, increased paralytic incidence
post-vaccine
few cases, all cases related to virus
8
Q
Piolovirus produces how many proteins?
A
one protein, causes self limited proteases
9
Q
How does poliovirus inject its +RNA genome into it?
A
injected after endocytosis, by utilizing hte capsid as an injection system
10
Q
What is the physiology of adenovirus?
A
latent virus in adenoides and tonsils, 51 serotypes, causes gastrointestinal or respiratory disease,
11
Q
What is adenovirus more dangerous in?
A
children and immunocompromised
12
Q
How does adenovirus attach and entry?
A
viral surfing by attaching to myosin, enters through clathrin mediated endocytosis, viral fusion pore control
13
Q
How is adenovirus shed from epithelial cells?
A
Enters throug apical end, shed on the basal side, and hte virus penton spike fiber disrupts adhesion gap junction to allow it back into the lumen
14
Q
How do you quantify infectious virus?
A
plaque assay
focus forming assay
single-step growth curve
15
Q
What are the basic steps in a viral life cycle?
A
attachment, penetration, uncoating, synthesis of components (synthesis of mRNA, translation of viral proteins, genomre replication),
assembly of viral components
exit maturation
16
Q
What is virion attachment?
A
for both naked and envelopoed virus, a viral surface protein recognizes a receptor on the target cell
17
Q
What is the receptor fro HIV?
A
Human CD4 on t cells
18
Q
What is the receptor on cell for EBV?
A
Human complement receptor CD21
19
Q
What is the receptor on cell for Rhinovirus?
A
Human ICAM1
20
Q
What is the receptor on the cell for Influenza virus?
A
sialic acid
21
Q
How do viruses cause disease?
A
Virus destruction of infected cells
viral modification of infected cell function
immune and inflammatory responses to virus infection
-fever,rash, myalgia
-immune-mediated damage or destruction
combination of several factors
22
Q
What innate response from host defense is responsible for viral combat?
A
soluble mediators (IFNs, cyokines, chemokines; antiviral response within infected cell; make surrounding cells resistant to infection, recruit effector cells) apoptosis
23
Q
What is the humoral adaptive response is sued to combat viral infection?
A
neutralizing antibody: block attachment or entry
complement fixing antibody: lyse virions or infected cells
24
Q
What is the cell-mediated adaptive response to combat viral infection?
A
MHC presentation of viral peptides killing of virus-infected cells by cytotoxic T cells
25
What are the characteristics of chronic virus infection?
Initial steps of infection similar to accute; however virus is not cleared. Initial robust immune response is subdued to prevent immunopathology; immune response of host set to a higher activation state overall
26
What is hte definition of a latent virus infection?
a viral cycle chaaracterized by minimal if any expression of a subset of viral genes and absence of lytic replication and infectious virion production
27
What is the prototype of latent virus infection?
herpesvirus
28
What are the innate immunity to viral infection?
```
Patterns by PRRs
Type 1 IFN secretion
cytokines -- IL1, TNFalpha
IFNgamma, chemokines
NK cells- direct killing of virus-infected cells by NK cells and NK cell are a huge source of IFNgamma
```
29
What are the order of immune responses for innate reaction to innate immune response?
Production of IFNalpha, IFNbeta, TNFalpha, IL12 early 2 day peak
NK cell mediated killing 3 day peak
T cell medaited peak 6 to 10 days
30
What is exogenous IFNalpha used to treat?
chronic Hep C
| tx melanoma, hairy cell leukemia, chronic myelogenous leukemia, Kaposi's sarcoma
31
What is exogenous IFN Beta used to treat?
used in treaatment of MS
32
Why is exogenous IFNgamma not used to treat disease?
limited clinical usefulness but side effects limit it's ability
33
What is PKR?
induced by IFN, protein kinase R
binds to ds RNA and becomes autophosphorylates; phosphorylates eIF-2alpha
inhibits translation
34
What is OAS?
2'-5' Oligoadenylate synthetase it is also induced by IFN
binds dsRNA
catalyzes synthesis of oligo adenlyate and activates RNAse L- endoribonuclease
35
IFNalpha and IFNbeta induce the anti-viral state which leads to waht?
increase surface class 1MHC
increased NK cells
decrease viral protein synthesis
36
What is the role of TNF?
tumor necrosis factor; a pyrogen which can induce fever
produced by activated macrophages, cD4 T cells and NK cells
induces death signaling
37
What is the role of IL1beta?
a pyrogen-can induce fever
| major pro inflammatory; produced and secreted by activated macrophages
38
What is IL6?
major pro-inflammatory cytokine
39
What is the role of NK cells?
```
kill targets after assessing the balance between inhibitory signals from class I molecules
activating signals from NK activating ligands
```
40
How are infected cells induced to undergo apoptosis?
from within; by internal factors and frm outside by Fas or TNFalpha, NK cells
41
What is the role of viral IFN-GammaR or viral IFNalpha/betaR?
blocks binding of IFN's and is encoded by poxviruses
42
How does Adenovirus inhibit PKR?
encodes its own structured RNA and inhbitis activation by dsRNA
43
How does poxvirus counter PKR activation?
encodes dsRNA binding proteins that sequester the dsRNA and prevent PKR activation
44
What cancer does hepatitis B and Hepatitis C cause?
hepatocellular carcinoma
45
What cancers do EBV cause?
lymphoma and nasopharyngeal carcinoma
46
What cancer does HHV8 cause?
kaposi's sarcoma KSHV
47
What cancer does HTLV1 cause?
adult T cell leukemia
48
What cancer does HPV cause?
cervical cancer; head and neck cancer
49
What patient population are virally caused cancers occurng
immunosuppressive
50
What does merkel cell polyoma virus cause?
merkel cell carcinoma a aggressive skin cancer in elder and immunosuppressed patients
51
What is the structure of papillomavirus?
member of paovavirus
infect cutaneous and mucosal epithelia
small circular double-stranded DNA genome
52
What proteins does the HPV genome encode?
virus encodes early and late genes?
E1 adn E2 mediate the replication and transcription of viral DNA
E4 disrupts cytokeratins to facilitate virus egress
L1 and L2 compose the capside
53
What are E5, 6, and 7 doing that is associated with onocogenesis?
E5-stim constitutive growth factor receptor signaling
| E6 and E7 neutralizes the major brakes that regulate the cell cycle p53 and Rb
54
What HPV protein neutralizes p53 and Rb to uncouple cell division?
E6 and E7
55
What HPV proteins stimulate growth factor receptor signaling?
E5
56
How does replication of HPV work?
early gene expression in basal layers
late gene expression in spinous and graunlar layer
virion assembled and released in cornified layer
57
Where is HPV virion assembled and released?
the cornified and granular layer
58
Where is late gene expression and viral genome amplifaction occuring in HPV?
granular and spinosis layer
59
Where is the early gene expression E1, E2, E6 and E7 occuring?
basal and spinous level of HPV
60
At what level does HPV initially infect,
the dermis
61
How does HPV E7 regulate Rb?
binds Rb and targets it for degradation so prevents it blocking the progression to S phase
62
What inappropiate entry into the cell cycle can activate p53 protein?
Induces production of Cdk/cyclin inhibitors and stops the cell cycle
63
What is the role of E6 protein of papillomavirus?
recruits a ubiquitin ligase that targets p53 for degradation and prevents it from blocking progression to S phase or inducing apoptosis
also induces the expression of telomerase
64
What is the role of a pap smear?
cytological evidence of diplasia or neoplasia; detection of koliocytotic cells which are rounded and appear in clumps
65
What is the role of hybrid capture assay?
used for detection, strain analysis, and quantification of HPV DNA
66
What is the virion structure and composition of retroviruses?
env protein is hte envelope
group specific antigens (gag)
Capid core is made of Matrix, Capsid, Nucleocapsid, protease
67
What are the 3 groups of proteins in a retroviral genomic RNA?
gag, pol and env
68
What does R stand for in retrovirus?
repeat on both ends of genome
69
What is the gag gene?
encodes the Matrix, capsid, nucleocapsid, and protease
70
What is the polymerase gene (pol)?
encodes reverse transcriptaseand integrase which are made as an extended polyprotein
71
What is the envelope gene?
encodes the env protein, which is made as a precursor and gets cleaved into different domains
72
Complex retrovirus HIV organized how?
similar to simple retrovirus except numerous adtional genes
73
How are the accessory proteins mRNA's generated in complex retrovirus?
complex alternative splicing
74
Replication cycle?
consists of a number steps seperated into two phases by the integration step
75
How does adsorption of HIV work?
HIV receptor is CD4/CCR5;
76
How does HIV penetrate and uncoat in human cells?
viral envelope fuses with cell membrane either at the cell surface or in endosomes after endocytosis
77
How does HIV uncoat in human cells?
genomic RNA is only partially uncoated, remains in a protein 'particle' particle in the cytoplasm
some of the gag proteins remian associated with incoming genomic RNA
78
How does reverse transcription work with HIV?
process of converting ssRNA to dsDNA; integrated DNA called provirus
79
How does integration work with HIV?
carried out by the integrase protein which enters cell with the virus and remains associated with the dsDNA
80
How does proviral transcription work in HIV?
major role of the LTR is to direct synthesis of viral RNA
organization of the LTR- U3 contains binding sites for cellular transcription factors acquired for high level RNA synthesis
81
How does RNA processing work in HIV?
as pol II transcripts all viral RNAs are polyadenylated, some must be spliced to generate teh env mRNA but a large portion must remain full length
82
How does translation occur in HIV?
most abundant protein is gag and gag-pol, made as a polyproteins from full length mRNA
83
What is the most abundant protein in HIV?
gag and gag-pol; initiates at an AUG start codon and ends at a stop codon
84
What does env protein is made from what?
spiced mRNA on ER-bound robosomes, moves through ER-golgi is inserted into plasma membrane
85
How does virion assembly and budding wokr in HIV?
how is the viral unspliced RNA selected for packaging instead of env spliced RNA or any other RNA
packaging: requires a psi signal; spicing removes psi signal
budding: viral gag and gag-pol polyproteins recruit RNA
maturation: as mentioned above proteolysis of gag and gag-pol by PR occurs after budding
86
How does retroviral mediated oncogenesis?
non-transforming retrovirus- non-acute or slow tumor viruses; tumors are caused by activation of inactivation of host genes
87
How does transforming retroviruses "acute" occur?
infections cause tumors within week; viruses harbor a mutated copy of a cellular gene involved in growth control
88
What six accessory proteins of HIV are required for replication?
Vif, Vpr, Vpu, Nef, Tat, Rev
89
What are the two regulatory HIV protein?
Tat and Rev
90
What is the HIV protein absolutely required for transcription?
Tat- transactivator of transcription
91
What does Rev do?
regulator of virion expression allows structural gene expression by promoting transport of unspliced RNA from nucleus to cytoplasm
92
What are restriction factors fo HIV?
viral proteins that overcome cellular defenses
93
What are teh two restriction factors of HIV?
Vif and Vpu
94
What does Vif of HIV do?
virion infectivity factor- causes a cellular antiviral protein to be degraded: otherwise is incorporated into new virion where block RT in the next cell by inducing massive viral dsDNA
95
What does vpu do in HIV?
promotes virion release from cell by inhibitin a host protien tetherin
96
What are the two co-receptors, which HIV bind one or the other of?
CCR5 and CXCR4
97
What are the presentl available drugs for HIV?
```
RT inhibitor
protease inhibitors
fusion inhibitor
entry inhibitors
integrase inhibitor
```
98
What is HAART?
highly active anti-retroviral therapy
considerablesuccess of cocktails triple terapies
long-term pts experience toxicity
99
Can dendritic cells become infected?
no can bind HIV but not productively infected; can assist in dissemination
100
What are the HIV tropisms?
M and T tropic
M infect macrophages in lab
T infect T lines in lab
101
What is the basis for starin tropisms?
env sequence of different HIV types
102
Which strain of HIV is most concerning?
M tropic bc source of person to person transmission
103
What is the mutation that protects against HIV infection?
32 bp deletion in CCR5; double mutation leads to no HIV binding
104
Co-receptor engagements triggers what?
a snapback of N and C terminal helices regions of gp41 which brings membranes together and fuses them
105
What are the indirect effects of HIV?
immune resposne kills infected cells, soluble gp 120 may bind uninfected cells and now susceptble to ADCC
106
What are the ways to diagnose HIV?
RNA RT-PCR
serology
Real time RT-PCR
107
What is the half life of infected memtory T cells?
greater than 5 years meaning you would require over 75 years to clear this department
108
what are some complications of influenza virus infection?
primary viral pneumonia
secondary bacterial pneuomnia
myositis and cardiac involvement
neurologic syndromes
109
How is influenza diagnosed?
rapid antigen capture, detects nucleoprotein
| RT-PCR
110
Adenoviruses cause what type of disease?
A very wide variety, GI, UTI, conjunctivitis, respiratory, lymphoid infection
111
What usually kills people when infected by measels?
pneumonia
112
What does mumps infect?
pancreas, parotid gland, ovaries, testes other glands can cause neurological issues
113
What is the host for mumps?
only humans
114
Rubella virus is what type of virus?
togavirus
115
What is the major concern from Rubella?
neonates younger than 20 weeks who are inected can result in congenital defects
116
What are the prominent clinical finding in congenital Rubella syndrome?
cataracts and other ocular defects, heart defects, death in first year
retardation
117
What is parvovirus B19?
single stranded DNA virus, icosahedral non-enveloped virus; dependent on host DNA replication functions
118
What is bocavirus?
newly discovered parvovirus responsible for GI and respiratory infections
119
Parvovirus infects what?
infects actively replicating red blood cell progenitors in bone marrow (viremia)
120
What are the clinical features of Parvovirus B19?
erytha infectiosum, bright red cheeks, maculopapular rash, circulating immune complexes
121
What are complications of B19 infection?
in chronic hemolytic anemia pts virus can cause aplastic crisus
when transmitted to fetus can cause still births and generalized edema
122
What viruses are transmitted by fecal/oral transmission in childhood?
rotavirus and norovirus
123
Rotavirus is what structure?
11 double stranded RNA segments with no envelope but a 3 layer capsid
group A most common cause of human disease
can have reassortment
Reovirus
124
What is the most imoprtant non-structural protein of hte rotavirus?
NSP4, an extotoxin that increases intracellular calcium leading to diarrhea due to disruption of tight junctions
125
What virus causes the largest number of sever diarrhea in children?/hospitalizations
rotavirus
126
What is teh concern with rotavirus vaccines?
```
protection
intussusception of intestines
viremia
immunosuppressed children
reversion
```
127
What is norovirus causing?
major cause of acute gastroenteritis in school-aged children and adults
128
What is the most common cause of foodeborne gastroentertiis in teh untied states?
norovirus
129
What are the symptoms of hand and foot disease?
mild fever, sore throat, fatigue, vesicular lesions on hand feet and inside mouth
130
What is the host of the hantavirus?
deer mouse
131
What is the disease associated with hantavirus?
hantavirus-induced pulmonary syndrome
132
What are two arthopod-borne viruses that are emerging?
West Nile and Dengue
three general type of disease fever
encephalitis
hemorrhagic fever
133
What is Dengue spread by?
mosquito, climate expaneded host range of vector
134
What allowed west nile to spread?
introduction of infected vector to new range
135
When was the first case of West Nile in the United states discovered?
1999
136
What is the natural resevoir of West Nile virus?
birds; only crows and Jays are affected negatively
137
Horse or humans are what for west nile virus?
usually dead end host, viremia is hard for it to achieve
138
What are the clinical features of west nile fever?
fever, fatigue, swollen lymph glands, headache, skin rash, eye pain
Severe disease in immunocompromised:
fever, ataxia, myelitis, GI sympoms, seizures, AMS
139
How is WNV diagnosed?
relies on hihg index of clinical suspicion; usually fall greatest number of human cases`
140
What is the first infection of dengeu fever described as?
breakbone fever, fever, muslce bone pain, joint pain
| not fatal have protection against reinfection with same serotype
141
What is the problem with getting a second infection of Dengue fever with different serotype?
antibodies that don't properly neutralize increase infections of Monocytes and macrophages, release inflammatory and can cause hemorrhagic fever
142
What is the diagnosis of Dengue done?
ELISA to detect antibodies
| using touriquette will result in broken vessels
143
What is the role of monkeypox?
relatively rare disease occuing mostly in Africa; virus a member of Poxvirus
first human case identified in 1970 not generally fatal
144
What are the symptoms of monkeypox?
incubation of 12 days
fever, headache, muscle aches, and backache
raised bumps
emergence is due to change in behavior and movemnt of virus
145
What are the symptoms of hantavirus?
fever, hemorrhage, 5-10%, headache, acute renal failure
146
When did hantavirus become aproblem?
during the korean war
147
Dengue virus is what type of virus?
a flavivirus
148
What are causes of Dengue shock syndrome?
300000 cases/yr
| occurs when individual with antibodies agianst one serotype is infected with another serotype
149
How is Dengue hemorrhagic fever diagnosed?
ELISA to detect antibodies to determine antibodies along witha positive tourniquet test
150
What is the cause of monkeypox?
relatively rare disease occuring in africa; small pox simlar but milder than smallpox
151
Monkeypox has what symptoms?
fever, headache, muscle ache, lymph nodes swollen, scab
152
what leads to developing and emergind diseases?
```
Change in demographics increased urban centers often with poor sanitation
increasd interntaional trade
increased international travel
Change in behaveior
-antibiotic, IV drug use, Promiscuous sex
Changes in environmen
change in tech
change in virust
```
153
What are the two emergin arborviruses?
west nile and dengue virus
154
When was west nile released into north america?
1999
155
What ar ethe features of severe west nile virus?
menigitis, encephalitis fever atazia myelitis GI symptoms seizures change in mental status
156
How is WNV diagnosed?
relies on high index of clinical suspicion
consider WNV in adults greater than 50 years of age or older
local WNV activity
vaccine availbe for horses
157
What are the gamma herpes viruses?
EBV
| Kaposi's Sarcoma
158
What are the Beta herpes viruses?
cytomegalovirus
roseolovirus
HHV-7
159
What are the alpha herpes viruses?
varicella zoster virus
| Herpes simplex virus
160
What occurs during the latent infection of the herpes virus?
Same strain of herpesvirus persists within the same host; Maintains itself as an episome
161
HSV-1 and 2 are latent at what points?
HSV-1 -- trigeminal ganglia
| HSV-2 -- sacral ganglia
162
Latency associated transcripts do what?
these are NEVER translated into protein and function to repress HSV gene expression by an unknown mechanism
163
Unknown stimuli trigger viral reactivation ccurs how?
few viral capsids are subjected to anterograde transport with mature virions produced around the site of innoculation-- reinfection of epithelial cells--lesion--spread: reccurent infection
164
Reinfection of a seropositive individual with a different strain of HSV is possible but uncommon, this is what?
an exogenous reinfection
165
What is the mechanism of action of acyclovir?
a suicide inhibitor: competes with dGTP for viral DNA polymerase
166
What is neonatal herpes?
inoculation during birth
inoculation during pregnancy results in multiple birth defects
dissemination replication
CNS is commonly affected
Disease usually manifests within days of life
mortality is high
survivors experience a very high rate of neurological abnormalities
167
What CMV in healthy adults presented?
mild mononucleosis or cold-like symptoms
| Asymptomatic in healthy adults
168
What are the leading causes of congenital birth defects?
TORCH
TOxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex
mild to severe mental retardation, deafness, death
169
What becomes symptomatic upon immunosuppression?
chemotherapy, organ transplant, and HIV
170
What long term persisten infection is associated with CMV?
atherosclerosis
immunosenescence
neuroblastoma
171
What are basic characteristics of CMV?
230 kbp double stranded DNA genome
-stages of gene expression; immediate early, early and late
expresses 750different proteins
enocdes its own DNA replication machinery
icosahedral
172
Cytomegalovirus transmission occurs how?
Direct contact with virus-containing secretions
inoculation onto a mucosal site
other routes
shedding with or without symptoms
173
What is the immune response to CMV?
Macrophage, interferon and NK cells control but insufficient to control
humoral doesn't play a role in clearance but limit reinfection or reactivation
cell mediated immune response is important up to 10%
174
What are the symptoms of CMV in healthy adults and children?
```
mild disease, often unapparent
fever, fatigue, sore throat headache
mononucleosis
liver function abnormalities
lymphocytosis
```
175
How is CMV diagnosed?
IgM or IgG although can be difficult to tell
owl's eye cells in urine or other tissues
culture virus from clinical material
PCR
176
How is CMV treated?
```
gangiclovir or valganciclovir
activated with phosphorylation by viral kinase inhibits viral DNA pol
Foscarnet
Cidofovir
Anti-CMV IgG
acyclovir is NOT effective
```
177
congenital CMV does what?
```
cause birth defects
first semester trimester infections have worse outcomes
poor outcomes if symptoms at birth
-petechial lesion
-small size at birth
-hepatoplenomegaly
Jaundice
permanent symptoms
hearing and vision loss
mental retardation
seizures
```
178
Who is CMV infection a problem in?
```
pregnant women
lifethreatening in
transplant patients
HIV patients
Immunosuppressive drug
pts undergoing chemo
```
179
What is the rate of seropositivity of EBV?
95% or greater by early 20s world wide
| a lot of asymptomatic infections
180
What are cahracteristics of EBV?
immediate early, early and late gene expression
replication in B cells or epithelial cells
latent infection in memory B cells
stimulate and immortalize B cells
181
What are the stages of EBV disseminationa nd latency?
transmission by blood and saliva
latency 3 occurs in proliferating B cells results in mononucleosis, post transplant lymphoproliferative disorder
latency type 1/2-viral antigens; can lead to Burkitt's, Hodgkin lymphomas, nasopharyngeal carcinoma
182
What are the EBV associated lymphomas?
Burkitt's lymphoma- b cell lymphoma of jaw and face
Nasopharyngeal epithalial carcinoma-EBV DNA in epithelial tumor cells
B cell lymphomas-Hodgkin and non-hodgkin
Immunosuppressed pts and transplant pts
183
What are the symptoms of EBV-mediated infectious mononucleosis?
```
5-20% of B cells infected
fever, malaise, lymphadenopathy, exudative pharyngitis, splenomegaly
symptoms due to T cell response
self-limiting
asymptomatic in young chilren
```
184
What is the disease post-transplant lymphoproliferative disorder?
EBV-mediate B cell proliferative disease
-immunosuppressive tx activates infection
-incidence 1-33% transplants depending on organ
within first year after transplant
donor B cells or reactivation in recipient
low risk if graft contains donor t cells
POOR PROGNOSIS 40-70% mortality
reduce immunosuppression
anti-CD20 antibodies eliminate B cells
185
How is EBV diagnsed?
serology
EBV mononucleosis
-test for heterophile antibodies by agglutination of animal red blood cells
PTLD-fluorescent in situ hybridization to EBER RNA in neoplastic cells
186
What is the is HHV-8?
Kaposis sarcoma herpes virus; causes Kaposi sarcoma, primary effusion lymphoma and multicentric Castlleman disease
replication occurs in CD19 peripheral B cells
187
What is the hepatitis A virus?
single serotype worldwide
fecal oral transmission
acute disease and asymptomatic infection
no chronic infecction
188
How often is jaundice causeed by Hepatitis A?
under 6 less than 10 percent
| over 14 yrs 70-80%
189
What are the complications associatedd with Hepatitis A?
fulminant hepatitis
chloestatic hepatitis
relapsing hepatitis
190
Who is the hepatitis A vaccine recommended for?
those traveling to areas with high incidence
ppl with chronic liver disease
infants
ppl working with HAV
191
Where are the hepatitis E outbreaks occuring?
US cases have travelt o HEV endemic areas and most outbreaks are associated with fecally contaminated drinking water
192
How does the outcome of hepatitis B infection change by age at infection?
chronic infections are the greatest in those infected at birth
symptomatic fnfections occur more regulary after about 4 years of age
193
What is the mechanism of hepadnavirus?
enveloped virus is bidning to sodium/bile acid contransporter
circular DNA genome partially double-sranded genome with DNA syntehsis occuring to form fully ds DNA and that goes to nucleus
mRNA "reverse-transcribedd" to ssDNA, DNA made partially ds
DNA can integrate into chromosome and remain in cell
194
HBV infected cell produce what two things?
infectious virus as well as non infectious HbsAg particles; antigen without DNA
195
What are the normal causes for initial infection by HBV?
```
mothers milk
vaginal secretion
blood
semen
saliva
so IDU, sex, neonatal, breast feeding
```
196
What are the symptoms of hepB?
```
fever,rash arthritis
Jaundice
Dark urine
malaise
anorexia
nausea
RUQ pain
itching
```
197
What are the normal clinical outcomes for HBV infection of adults?
90% have full resolution
9% have HbsAg+ for greater than 6 motnhs ; 50% of those resolve the rest have some osrt of chronic state which can result in carcinoma or cirrhosis
1% fulminant hepatitis
198
What is hepatitis delta?
viroid that can only grow in hepatits B infected cells
small RNA copied by host RNA pol II, catalytically active ribozyme that processes itself
encodes 1 antigen becomes packaged in Hep B sAg
199
What are the clinical features of Hepatitis D?
coinfection; sever acute disease and low risk of chronic infection
superinfections(subsequent to HBV) usualy develop chronic HDV and high risk of sever chronic liver disease
200
What is the treatment of HBV?
vaccination is key to prevent infection of high-risk individuals and infants
polymerase inhibitors, nucleoside analogs, IFN-alpha; aka antivirals
new approaches silence HBV expression during chronic infection
201
Hepatitis C is what structure?
flavivirus; pos strand, RNA virus. Enveloped virions
9 kB genome; 10 proteins, involves proteolytic processing
many quasi-species
encodes multiple immunomodulators
liver damage primarily due to immunopathology
hihg incidence of chronic and asymptomatic infections
assoicated with hepatic carcinoma
202
What is the viral life cycle of hepatitis C?
hepatocyte specific- basis for developing therapies
intimate relationship with intracellular lipids and membranes
RNA replication; IRES-mediated translation
proteolytic processing
membrane associated RNA replication
assembly
maturation and release
203
What are the most common sources of Hep C infection?
60% IVDU
| 15% Sexual
204
What are teh clinical outcomes of HCV infection of Adults?
```
15% resolution
85% persistent infection
--6% liver failure
--20% cirrhosis
--4% hepatocellualr carcinoma
```
205
Why does HCV lead to a high incidence of carcinoma?
HCV core proteins interact and regulate many tumor suppressors; induce steatosiss
envelope protein E2 inhbiits NK cells
non-structural proein NS3 can enhance cell growth
NS5A enhances cell growth and prevents apoptosis
206
How does the IL28B gene playa keyaoutcome in HCV infectin?
it encodes IFN-gamma and a polymorphism has a strong impact on teh response to IFN therapy as well as natural clearance; the primary genotye in the US has more trouble clearing
207
What makes a virus an inmportant feasible target for vaccine development?
infection is serious enough
limited number of serotypes
virus doesn't mutate rapidly
natural infection is acute and self-limiting and immunity is long-lasting
