Fenger Flashcards
1
Q
What is a latent virus? Example?
A
- a virus that has been integrated into the host genome and can become reactivated at a later date.
- Herpesvirus family
2
Q
What patient population can herpes be especially devastating for?
A
immunocompromised
-HIV, Cancer, Chemo, Transplant
3
Q
What are in the alpha Herp family?
A
HSV, VZ
4
Q
Type of genomic material for herp? Configuration?
A
- Double stranded DNA wound around protein core
- configured with 4 different arrangement of Ul and Us regions
5
Q
Does the herpes family have a capsid or envelope?
A
Both. Icosohedral capsid made of capsomers. Envelope with glycoprotein spikes
6
Q
Which type of HSV is tranmitted genitally mostly? How is the other type transmitted?
A
- HSV2
- HSV1 is transmitted orally generally
7
Q
What are the primary diseases of Herpes? (Big notecard)
A
- Mouth(HSV-1): Gingivostomatitis-vesicular lesions all over oral cavity
- Eyes(mostly HSV-1): Dendritic Keratitis- infection of the cornea of the eye
- Skin(HSV-1): Gladiatorum- occurs in sweaty spots; Herptetic Whitlow- fingers/dentists; cold sores; herpeticum eczema
- CNS: Children(HSV2): infected birth canal from some skanky mom tranmits to neonate brain through blood. VIREMIA
Adults(HSV1): spreads in from olfactory nerve and infects temporal lobe. NEUROGENIC
8
Q
Typical ways to acquire HSV 1 and 2?
A
HSV1- usually acquired as a child and inapparent for first 6-18 months. Check Ab for evidence infection has occurred at some point
HSV2- acquired after Jacobs balls dropped and he learned that his penis had a purpose other than making shadow monsters on the wall at night…AKA getting that poon tang and exchanging sexual fluids raw dawg style
9
Q
Herpes Virus travels along ____1_____ to reach the _______2_______for HSV1 and _____3_____ for HSV2
A
- nerves
- Trigeminal Ganglia
- Sacral Ganglia
10
Q
What factors can cause herpes reactivation despite AB presence and cell mediated immunity?
A
Host hormonal changes, chemotherapy, mal functionaing immune system, aging, UV light
11
Q
Why dont lymphocytes and other immunity cells kill the latent virus?
A
- the latent virus is sequestered away from the immune system as it lays dormant in the ganglia.
- when it becomes reactivated it travels along the axon to the original site of infection where the immune system can now respond and cause symptoms.
12
Q
How does occular herpes cause blindness?
A
Repeat occurrences can cause stromal scarring with every inflammatory healing process
13
Q
What percent of adults have been infected and what fraction of them will have recurrent disease?
A
70-90 percent have been infected and 1/3 to 1/2 will have recurring disease
14
Q
What cancer is HSV2 potentially linked with?
A
suspected to be indirectly linked to cervical cancer but potentiating the papilloma virus’ cancer causing ability.
15
Q
What branch of adaptive immunity is important for resistance to HSV and which branch is important for recovery from infection?
A
- Ab is important in resistance
- Cellular immunity is important is recovery
16
Q
Types of vaccines for Herpes
A
- Liv Attentuated: will induce a cell mediated and antibody response
- Killed: Will give just an Ab response
- Split Vaccine: a killed purified bundle of viral antigens (subunit vaccine)
17
Q
HSV recurrence can initiate what 2 sequelae?
A
- Erythema multiforme: 75% of the time is due to HSV recurrence
- Idiopathic neuralgia: bells palsy, trigeminal neuralgia, epileppsy
18
Q
Flashback: What Nerve is damaged in Bells Palsy?
A
Cranial Nerve 7. Thats the facial in case keegan forgot.
19
Q
Tzanck Smear?
A
- Test for Herpes
- Scrape cells from the base of the lesion, stain and look for nuclear inclusions
20
Q
What type of sample is best for HSV virus isolation in a cell culture
A
- fluid from the vesicle
21
Q
When Jacob is making his OBGYN rotation he will likely at some point see a late term pregnant woman with a herpetic lesion her puss. What should jacob recommend?
A
Jacob should suggest the baby be delivered via C-section to avoid neonatal infection of fetus brain and visceral organs.
22
Q
What anti viral drug class do the acyclovir family fall under?
A
nucleoside analogs
23
Q
Acyclovir MoA and use?
A
-reduces the severity of recurring Herpes infection.
-inhibits viral DNA polymerase by blocking it progression on the DNA
administered as prodrug and activated by viral thymidine kinase and cellular kinase to become triphosphate.
24
Q
Valacylovir advantages?
A
taken orally and absorbs better than acyclovir
25
How does foscarnet work>
inhibits viral DNA polymerase by binding to it
26
Two mechanisms mutants use for anti-viral resistance?
1. alter DNA polymerase gene so protein can no longer bind (foscarnet)
2. alter thymidine kinase gene so it no longer phosphorylates (acyclovir)
27
What agents inactivate infectious virus?
Chloroform, ether, glutaraldehyde, detergents
| -All act to destroy virus envelope
28
What is the typical primary infection for Varicella?
Chicken pox
29
What type of DNA does VZ have?
Double stranded DNA
30
How do the lesion of VZ and small pox differ?
VZ- successive crops in specific area
| SP- one crop of lesions in a specific area
31
What are common complications seen in adults and children with VZ infections?
Adults: pneumonitis causing x-ray calcified nodules in lung
Children: encephalitis (2X more in males); hemorrhagic varicella (bleeding vesicles)
32
What drug is reyes syndrome related to?
apirin
| -dont give while VZ infected b/c of hepatic failure and encephalopathy
33
What is Shingles? How does it present? Where is it latent?
- Recurrent infection of VZ
- present as unilateral lesions following a dermatome
- lies latent in dorsal root ganglia: Thoracic > Ophthalmic > Lumbar > Cervical
34
How does VZ initiate primary infection?
Respiratory mucosa --> viremia --> skin (macular papular, non umbilicate vesicles
35
VZ incubation period?
2 weeks
36
When are most people first infected with VZ?
Children 6-8 yo
37
Causes of VZ reactivation?
X-rays, tumor in CNS, trauma, immunosuppression, reexposure to VZ
38
How are zoster lesions typically treated?
Zoster Ummine Globulin to help prevent comlications. Given IM 2-3 days within exposure. Ab neutralizes virus
39
Zoster Vaccine?
- licensed in 1995
| - attenuated live virus given to kids twice at 12 months and against at 4-6 years
40
Varivax vs Proquad
Varivax- single antigen VZ vaccine
| Proquad- vaccine for measles, mumps, rubella, and varicella
41
Zoster Vaccine for old people?
Zostavax- for those over 60 years old reduces likelihood of shingles by 50%
42
What is the treatment for immunocompromised patients with V or Z?
For adults adenine arabinoside along with oral acyclovir (valacyclovir?)
For Children IV acyclovir
43
Orthomyxoviridae are responsible for what type of virus?
Influenza Type A B and C
44
What are the possible hosts for the Influenza types?
A- humans, swine, avian, equine(or horses for keegan)
B- human
C- human
45
What is the genomic composition in orthomyxo?
- single stranded RNA with - polarity (complimentary to mRNA)
- must first convert to mRNA with + polarity to serve as messanger
46
How is the outter viral structures on orthomyxo arranged?
- helical nucleocapsid compased of RNA helix plus NP, PB1, PB2 and PA
- all helical capsids have an envelope accompanying. This envelope has 2 glycoproteins.
47
What are the Glycoproteins associated with the influenza envelope?
H (hemagglutinin), N (neuroamidase)
These are both strain specific AgS
48
What type of polymerase is associated with influenza? Where is it located?
RNA dependent RNA polymerase which gets stored in the helical nucleocapsid.
49
What critical step in orthomyxo viral replication is RNA-RNA polymerase able to do?
- create +RNA from -RNA
| - cant use host polymerase bc host doesnt have necessary machinery
50
What are the influenza antigens?
Nucleocapsid- capsid around the RNA helix
M protein- matrix protein beneath envelope
H protein- detected by hemagglutination, neutralization, C-fixation
51
What is the stepwise process of viral orthomyxo replication?
1. Attachment of viral particle to cell surface receptor. Mediated by H protein binding sialic acid containing receptors
2. Virus penetrates by endocytic process and enclosed within a vacuole.
3. Acidic vacuole causes H protein to fuse vacuole membrane with virus envelope
4. Acidification of the capsid causes viral genome release in cytoplasm
5. viral RNA along with associated RNA polymerase travels to nucleus
6. transcription of viral genomic RNA and mRNA begins
52
For orthomyxo what is the progression of RNA polarity through replication?
Genomic RNA enters the cell with - polarity ---> copied to several + strands ---> new +strands can act as either mRNA and use host machinery to make viral proteins or it can be used as a template for more - polarity genomic RNA
53
In influenza, what is the difference between viral RNA templates and RNA transcripts?
- the transcripts (+) are 20-30 nucleotides shorter than corresponding template (-) RNA
- the +mRNA will have a polyA tail attached to 3' and a cap donated by cellular mRNA to the 5' end
- allows the (-) strand to continuously be used as a template for new m RNA
54
In influenza after +mRNA is transcribed what happens?
- the mRNA will exit the nucleus and enter the cytoplasm
- H and N mRNA's are translated while entering the ER while the other proteins are translated in the cytoplasm
- H and N accumulate on the golgi surface where budding will occur
55
What is a replicative intermediate in orthmyxo?
-an RI is the +RNA that is transcribed from the genomic -RNA and serves as a template for many more genomic -RNA to be transcribed
56
What are the three components of the orthomyxo virus capsid?
1. -RNA
2. helical Capsid proteins
3. RNA-RNApolymerase
57
Once the nucleocapsid proteins have been translated what must happen to form new virus progeny?
- the 8 nuclecapsid proteins must migrate to the portion of the cell membrane that have accumulated H and N proteins
- budding occurs and the virus acquires its envelope
58
What protein must be cleaved to make viral particles infectious?
H protein
59
What is the function of neuroaminidase?
- role in the budding of progeny virus
| - lowers the mucous viscosity during infections
60
What is the antigen in influenza that induces the highest immune response in the host?
H protein
| -11 H subtypes
61
How many N subtypes?
8 N subtypes
62
Define antigenic drift?
- H and N protein variations due to point mutations
- drift leads to epidemics
- existing ab with the human may not effectively neutralize the virus
63
Define antigenic shift?
- shift occurs when an animal population gets infected with both the animal version of the virus and the human version of the virus
- H protein variations occur when reassortment occurs between the two versions creating an entirely new antigen
- causes pandemic
- prexisting abs are ineffective at neutralizing
64
What is antigenic sin?
each new infection of influenza only bolsters the memory Ab population sensitive to the antigen that induces the strongest immune response.
65
What is the genome of picornaviridae?
single stranded non segmented (+)RNA
| this allows naked genomic DNA to transfect the host cell
66
What are at the two ends, 3' and 5', of the picorna RNA?
the 3' end has a polyA tail
the viral 5' end has a non cap structure VPg
67
What is the shape and how many proteins are in the picorna capsid?
icosahedral capsid consisting of VP1 2 3 and 4 proteins with no envelope
68
Which picorna virus is stable to acid and which is not?
Enteroviruses are stable while rhinoviruses are not
69
What protein is lost from picorna when it binds the cell receptor?
love the VP4 protein
70
What type of penetration does picorna show?
endocytosis (viropexis)
71
Where are VP1 VP2 and VP3 removed?
cytoplasm causing the RNA genome to be relased
72
Where does viral genomic RNA replication occur in the picorna virus?
cytoplasm
73
What sequence on the 5' end is critical for the +mRNA to be translated?
The Internal Ribosome Entry Site
74
How does translation of multiple proteins work in the picorna virus?
the formation of polyproteins occurs
- many viral proteins linked together into one continuous large protein
- the polyprotein made is P123 and is a precursor protein
75
What is P123 cleaved into?
After being broken into P1 P2 and P3 structural polypeptides and enzymes will be made.
P1= VP proteins
P2= proteases
P3=VPg and 3D (polymerase)
76
What are picorna +RNA with and without VPg used for?
With VPg its used for RNA replication
Without VPg its translated and proteolytically cleaved
77
What does picorna virus use for genomic replication?
Replicative Intermediate: the mRNA w/ VPg is copied into many -RNA and then many new +RNA w/ VPg is tranlated from the -RNA template
78
During the creation of picorna virus progeny are there more mRNA or capsids made?
Far more capsids made.
- empty capsids released but there are not infectious
- 10,000 infectious virus particles can be released per cycle
79
What is unique of the retroviridae family?
they contain reverse transcriptase which is unique in its ability to crate DNA from RNA template.
80
Subfamilies of retroviridae?
Oncovirinae (tumor virus), Lentivirinae (slow virus AIDS), Spumavirinae (foamy and syncytial virus neurodegenerative diseases)
81
What is the capsid structure of retro and how many proteins are involved?
- complex structure: helical nucleocapsid plus a cylindrical icosahedral capsid around the outside
- 4 internal capsid proteins (GAG)
82
What makes the genome of retro virus?
SS RNA made of 2 identical 35S RNAs joined by cellular tRNA
| -Diploid genome
83
What is the enzymatic complex associated with retro?
complex of proteins consisting of RNA dependent DNA polymerase(reverse transcriptase), DNA polymerase, RNAse H and integrase
84
Is there a envelope in retro?
yes there is
- it is formed from the budding from a cell membrane
- 3 envelope proteins encoded by ENV gene
85
What is the order of genes on the RNA genome of retro?
GAG - Pol - Env - (+/-)ONC
-chronic leukemia viruses lack ONC
86
how do the genes of acute leukemia/sarcoma viruses typically differ from chronic leukemia? What is the sarcoma exception?
- Chronic leukemia viruses lack the ONC gene
- Acute leukemia/sarcoma usually lacks the ENV gene but has the ONC gene
The exception is Rous Sarcoma which has all the genes
87
What does the HIV RNA genoma have?
GAG-POL-ENV-plus another coding region
88
Where does replication of a retro virus occur?
in both the cytoplasm and the nucleus
89
What is the general pathways in terms of polarity and type of genetic material involved in retro replication?
+RNA genome ---> -DNA --->+DNA (provirus)
90
What is a provirus?
- a provirus is the +DNA formed during replication that uses integrase to become integrated within chromosomal DNA
- formation of a provirus take place in the cytoplasm then transported to the nucleus for integration
91
What does proviral DNA gain when it is made from genomic RNA?
Long Terminal Repeats (LTRs) are located the end of each provirus
-LTR has regulatory regions within it which bind regulatory proteins
92
Where is a provirus replicated and where is it integrated?
replicated in the cytoplasm
| integrated in the nucleus
93
Within the retrovirus genome where are the integrase and the protease coded?
within the Pol region
94
What is the function of RNAse H?
- chew up the genomic RNA that was used as a template to make -DNA.
- the mRNA has to be removed from the -DNA because a +DNA must be transcribed to make the ds DNA provirus
95
What are the steps for a retrovirus to get from genomic RNA to ds DNA provirus and where do the enzymes involved work? Name those enzymes.
1. Preceding this is the process of attachment, penetration and uncoating
2. Free viral genomic RNA is released into the cytoplasm
3. viral RNA-DNA polymerase transcribes a -DNA on the +gRNA
4. viral RNAse chews up the gRNA template to free the -DNA
5. free -DNA is used as a template for DNA-DNA polymerase to make ds DNA (Provirus)
96
How reliable and accurate is the reverse transcriptase process in retrovirus?
very error prone
97
Once provirus has been integrated into the cellular genome what are the order of genes on the provirus from start to finish?
LTR - GAG - Pol - ENV - ONC - LTR
98
What mRNA's are made from provirus and what proteins are synthesized from that mRNA?
35s mRNA- GAG pr GAG-Pol polyprotein
28s mRNA- ENV polyprotein, polyprotein cleaved to smaller proteins
21s mRNA- ONC protein, present in acute leukemia and sarcoma virus
99
What gene encodes the protein responsible for the proteolytic cleavage of polyproteins into viral proteins
- PRO gene encodes for the protease enzyme
| - PRO gene is usually associated with the Pol gene on the genome
100
What are RNA viruses capable of doing the DNA viruses cant regarding life cycle of virus?
- DNA viruses cause the cell to become lytic OR lysogenic
| - RNA viruses can integrate andcause the cell to become lytic AND lysogenic
101
How do chronic leukemia viruses cause leukemia when they are missing a ______1_____ gene?
1. ONC- chronic leukemia virus have no ONC
- they are still able to cause leukemia by integrating close to a protooncogene that already exists in the cell. When they integrate by it the LTR's regulatory regions can turn on the prexisting protooncogene.
102
How do chronic leukemia viruses behave in vitro? in vivo?
In vitro- no transformation
In vivo- activates a leukemia protooncogene after a long latent period
103
How do acute leakemia-sarcoma viruses behave in vitro? in vivo?
In vitro- Transformation occurs but no virus is produced. Rous Sarcoma is exception and does make virus in vitro
In vivo- sarcoma
104
Do chronic and acute leukemia viruses have envelopes?
Chronic has a non defective envelope but acute leukemia viruses lack the ENV gene (except Rous sarcoma)
105
What do acute leukemia viruses require to produce more virus particles?
- they require a helper virus for replication
| - another virus needs to supply the ENV proteins for evelopement
106
Transformation of a cell into a cancer or tumor cell requires what?
oncogene
107
What is the origin of protooncogenes?
-usually found originally in the human or animal population somehwere
108
How does a protooncogene become an oncogene?
- If an oncogene is made of DNA regions designated O, N and C then protooncogene within the human or animal population also has O, N and C regions but they are separated by intronic sequences
- when they are incorporated into the viral genome the introns can be lost and the O,N and C regions are brought together to form ONC.
- Point mutations will occur in each region along the way
109
What are the 4 mentioned methods for turning on a suppressed protooncogene?
1. chemical carcinogen can cause a mutation in the repressor gene causing a faulty repressor protein
2. LTR of an inserted leukemia provirus near a protooncogene turns on gene
3. translocation of the protooncgogene from one chromosome position to another. The new location can be close to an operator or activator of another gene
4. overdose of onogene proteins from acute leukemia infection
110
***** Know this card****
| What type of protein is made from the translation of oncogenes?
- the majority of oncogenes encode for tyrosine kinsases
| - unregulated phosphorylation of tyrosine residues causes the oncogenicity of the cell
111
How do tumor suppressor genes work and what are some examples of proteins they encode for?
-the two most common tumor suppressor proteins are Retinoblastoma and p53
- they work by the two hit hypothesis
- mutations must occur in both alleles one mutation can be inherited
112
during the cell cycle what is the normal process of phosphorylation for the Rb protein.
- a normal Rb protein with go from phophorylated to dephosphoylated during the cell cycle
- mutations in Rb gene may cause the Rb protein to interact poorly within the cell cycle
113
Other than mutations within the Rb gene how else can its function be lost?
-other DNA viruses can generate products that bind Rb and prevent it from functioning.
