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ID Week 1 > ICL 1.12: Parvo, Papova & Poxviruses > Flashcards

ICL 1.12: Parvo, Papova & Poxviruses Flashcards

1
Q

what type of virus are parvoviruses?

A

naked DNA virus

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2
Q

what type of viruses are polyomaviruses?

A

naked DNA virus

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3
Q

what type of viruses are papillomaviruses?

A

naked DNA viruses

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4
Q

what type of viruses are poxviruses?

A

enveloped DNA viruses

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5
Q

which viruses are associated with cancers?

A
  1. papillomaviridae
  2. herpesviridae
  3. hepadnaviridae
  4. retroviridae
  5. flaviviridae

the cancers are usually cancers of the cells that the virus infects; it’s because the virus is changing the cell programing to keep them dividing

also the viruses are usually very specific for a certain type of cancer

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6
Q

which cancers are associated with the papillomaviridae family?

A

virus: human papillomaviruses

benign disease: benign warts

tumor: cervix, skin, anus, penis

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7
Q

which cancers are associated with the herpesviridae family?

A 
#1
virus: EBV

benign disease: infectious mononucleosis

tumor: Burkitt’s lymphoma, Hodgkin’s lymphoma, B lymphoproliferative disease and nasopharyngeal carcinoma

#2:
virus: Kaposi's sarcoma-associated herpesviruses

benign disease: Castleman’s disease

tumor: Kaposi’s sarcoma, body cavity lymphoma

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8
Q

which cancers are associated with the hepadnaviridae family?

A

virus: HepB

benign disease: hapatitis, cirrhosis

tumor: hepatocellular cancer

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9
Q

which cancers are associated with the retroviridae family?

A

virus: human T-lymphotropic virus 1

benign disease: tropical spastic paraparesis

tumor: adult T cell lymphoma

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10
Q

which cancers are associated with the flaviviridae family?

A

virus: HepC

benign disease; hepatitis, cirrhosis

tumor: hepatocellular cancer, lymphoma

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11
Q

what are papovaviruses?

A

polyomaviridae and papillomaviridae were formally called papovaviruses

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12
Q

what is SV40?

A

polyomavirus

SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans

like other polyomaviruses, SV40 is a DNA virus that has the potential to cause tumors in animals, but most often persists as a latent infection

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13
Q

why is SV40 historically important?

A

SV40 is a polyomavirus that was the first DNA tumor virus isolated

studying it led to the concept of tumor antigens (T-Ag), oncogenes acting on cell p53 & RB to induce cells to divide, the nature of first eukaryotic promoter, splicing, first vector for introducing genes into cells, etc.

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14
Q

what are the general characteristics of the polyomavirus?

A

naked, icosahedral virion

very small genome

*circular dsDNA

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15
Q

how does the polyomavirus replicate?

A

this is a small circular dsDNA virus so there will only be E and L genes, no IE genes

the virus needs to get to mRNA so they will have highly active promoters that are recognized by transcription factors in the host

host RNA polymerase will transcribe a long primary transcript from the E region which is spliced into 2 mRNA – there are 2 possible splicing sites

the first splicing site creates a longer mRNA which leads to translation of a larger protein called large T antigen (T-Ag)

then the alternative splice site doesn’t remove a premature stop sequence so when you splice here, you get a smaller protein called small T antigen (t-Ag)

T-Ag and t-Ag are viral proteins that are very good at transforming cells to inactivate tumor suppressor genes so that the host cell will keep replicating

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16
Q

what does p53 do?

A
  1. it is a tumor suppressor that is mutated or abnormally expressed in many human cancers
  2. it allows cells to repair DNA damage or die by apoptosis
  3. it binds to DNA and activates or represses many genes
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17
Q

how do T-Ag and t-Ag interact with p53?

A

they are E genes products expressed in the polyomavirus!

T-Ag and t-ag from SV40 polyomavirus are precipated out and interact with p53 in the host cell

these viral proteins bind to the host p53 protein and inactivates it so that the virus can better replicate in the cell

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18
Q

what does T-ag do?

A

it’s an E gene product of polyomavirus that:

  1. induce cells to proliferate if they are in G0
  2. forms complexes with largest subunit of DNA polymerase a, p53 tumor suppressor protein, and p105RB + RB-related proteins
  3. turns on viral DNA synthesis
  4. binds to ori (origin of replication)
  5. turns on transcription of late genes turns off transcription of early genes
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19
Q

what does t-Ag do?

A

small t-Ag works with the large T-Ag in transformation of cells. Its targets are different: t-Ag binds a cell protein phosphatase and can activate pol II and pol III transcription

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20
Q

what are the two main human polyomaviruses?

A
  1. JC virus
  2. BK virus

70-80% of adults have antibodies to BK and JC viruses!! so most people have actually been exposed to this virus but only in immuno-compromised patients will it cause a problem

primary infection is in childhood

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21
Q

what is JC virus?

A

a polyomavirus = small naked virus with circular dsDNA

JC = John Cunningham virus

the hallmark of this virus is that it causes progressive multifocal leukoencephalopathy (PML)

PML is a demyelating disease so it kill oligodendrocytes that produce myelin for the CNS and it’s progressive so patients who get it will die within a few months

PML patients will have non-enhancing multifocal brain lesions in white matter that can be seen in brain imaging

only effects people where CD4+ < 200 like in HIV patients

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22
Q

what is BK virus?

A

a polyomavirus = small naked virus with circular dsDNA

BK causes nephropathy and other urinary tract problems like hemorrhagic cystitis –> this usually happens in kidney and BM transplant patients

mild respiratory illness common in renal transplant patients too

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23
Q

what are the clinical features of polyomaviruses?

A

polyomaviruses produce inapparent infections in natural hosts but are oncogenic in species different from their natural host

currently, polyomavirus-associated nephropathy (PVAN) is a serious, emerging complication in renal transplant recipients

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24
Q

how do you diagnose polyomaviruses?

A

PCR for genome DNA and ELISA for antibodies

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25
Q

when would you do RT-PCR?

A

for RNA viruses

you would use it to convert RNA to DNA

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26
Q

how do you treat polyomaviruses?

A

no vaccines or antivirals currently available….

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27
Q

what are the characteristics of the papillomavirus?

A

small, naked icosahedral virion

circular dsDNA

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28
Q

what is the hallmark presentation of human papillomaviruses?

A

warts! aka papillomas lol

papillomaviruses cause papillomas in natural hosts and are implicated in epithelial-derived cancers in several animal species, including humans

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29
Q

how does HPV replicate? (human popullomavirus)

A

HPV has a unique niche where they replicate only in replicating epithelial cells and this makes it hard for them to infect cells

the virus has to find a way to get to the right cells to cause an infection – in a normal epithelium we have columnar cells that are alive and replicating and as the cells replicate and head outwards they differentiate and become less of a cell because they lose their nucleus and become your skin!

HPV needs to replicate in the live cells, not your dead skin cells and the way the get to the deeper skin layers that are replicating is by a scratch in your skin that introduces the virus to the cells

so once the replicating cells are inflected, they will make E genes, which for the papilloma viruses these are E7 and E6 which bind to and inhibit p53 and RB = cell keeps replicating

as the cells differentiate towards the outside layers of skin, you get L gene expression

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30
Q

how does HPV cause warts?

A

warts are just extra cell growth

this is caused by early gene produces E6 and E7 which bind to and inhibit p53 and RB, respectively

p53 and RB are the cellular safeguards that are checkpoints in the cell cycle

so transcription of early genes and translation of early proteins induce a steady state of viral DNA synthesis and proliferation of basal and suprabasal epithelial cells

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31
Q

what are the clinical features of HPV?

A
  1. verrucae vulgaris = cutaneous common warts
  2. condyloma acuminata = genital and anal warts
  3. epidermodysplasia verruciformis

think Treeman for worst case scenario of HPV…

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32
Q

what is epidermodysplasia verruciformis?

A

a skin condition caused by HPV that often becomes cancerous

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33
Q

how do you diagnose HPV?

A

we CAN’T grow HPV in a tissue culture, it can only grow in those happy replicating skin cells which are hard to reproduce

this means we CAN’T serotype HPV

so to diagnose, you have to look at the genome, sequence it and do PCR

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34
Q

how do you proclaim a new strand of HPV?

A

clone the HPV genome, radioactively labeling it and crosshydridizing to reference HPV DNA — if less than 50% of laveled genome is protected by binding to the reference HPV DNA then it is a new type of HPV

if the nucleotide sequence of a short highly conserved region found in all HPVs varies by more than 10% from that in all other known HPVs, the isolate is defined as a new type, or more accurately, as a new genotype

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35
Q

what’s the difference between serotype and genotype?

A

a serotype is based on antibody recognition of the virus during the infection

the antibodies can be used to recognize the virus if we purify them

however, antibdoes can recognize multiple viruses so you won’t be able to differentiate closely related viruses

genotyping on the otherhand is very specific and you can differentiate

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36
Q

which HPV strains are high risk?

A 
16
18
31
33
35
45
52
58
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37
Q

which HPV strains cause plantar warts? is there a risk of cancer?

A

1 and 4

no risk of cancer

plantar warts on sole and palm

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38
Q

which HPV strains cause common warts? is there a risk of cancer?

A

2 and 57

no risk of cancer

cutaneous and genital warts

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39
Q

which HPV strains cause flat warts? is there a risk of cancer?

A

3 and 10

no risk of cancer

cutaneous and gential warts

40
Q

which HPV strains cause epidermodysplasia verruciformis? is there a risk of cancer?

A

5,8 and 47

super high risk of cancer!!!

epidermodysplasia verruciformis on the face, trunk and esophagus

41
Q

which HPV strains cause benign warts? is there a risk of cancer?

A

6 and 11

low risk of cancer

anogenital and larynx benign warts!!

larynx benign warts = laryngeal papillomatosis (acquired during childbirth)

anogenital benign warts = condyloma acuminata (acquired during sex)

42
Q

which HPV strains cause flat condylomata or carcinoma? is there a risk of cancer?

A

16 and 18

high risk of cancer

anogenital and esophagus cancer

HPV 16 and 18 cause anogenital squamous cell carcinoma bceause HPV infects squamous cells found in the skin and anus and cervix

43
Q

what’s important about HPV 6 and 11?

A
  1. can cause laryngeal papillomatosis = recurrent respiratory papillomatosis which is when tumors develop in the airways, usually of children (acquire
  2. they are also found in pre-malignant lesions of the cervix -the so-called cervical intraepithelial neoplasia (CIN) which are graded I to III

however, neither HPV 6 nor 11 have been found in malignant lesions of the cervix

44
Q

what’s important about HPV 16, 18, 31 and 33?

A

they are frequently found both in CIN and invasive squamous cell carcinomas of the cervix!

we are most concerned about these strains!!

infections by type 18 are less common than type 16 but more aggressive

45
Q

why do we care which HPV genotypes are associated with malignancy?

A

because these are the strains that we are going to develop drugs for!

46
Q

how do you make an HPV vaccine?

A

we make vaccines from the capsid of the HPV virus!

if you take the capsid proteins from a virus and put them in a tissue culture, the capsid proteins will spontaneously crystallize – you can then turn this into a vaccine because when you inject the capsid proteins into us, our body will develop antibodies against the capsid proteins without actually infecting us with the virus

so then when we are exposed to the real virus, we will recognize its capsid proteins and be able to fight it

47
Q

what is the most common STD in the US?

A

HPV

48
Q

how common is HPV?

A

it’s the most common STD in the US

but most infections are latent or subclinical

25-45% of sexually active women are positive by PCR for HPV but only 10% of HPV-positive women show signs of infection by Papanicolaou (PAP) smears

49
Q

how do you prevent HPV?

A
  1. Gardasil

2. Cervarix

50
Q

which HPV strains does Gardasil protect against?

A

HPV 16, 18 (70% of cervical cancers)

HPV 6, and 11 (90% of genital warts)

it’s made from non-infectious HPV-like particles (VLP) and is an inactivated subunit vaccine!

it doesn’t contain thimerosal/mercury

doesn’t cover 31 and 33 but we’re working on it

51
Q

which HPV strains does Cervarix protect against?

A

HPV 16 and 18

52
Q

what are the two subfamilies of the poxviridae family?

A
  1. entomopoxvirinae = poxviruses of insects

2. chordopoxvirinae = poxviruses of vertebrates

53
Q

what are the general characteristics of the poxvirus?

A
  1. largest and most complex animal viruses
  2. virions are complex, oval or brick shaped, with a core and lateral bodies
  3. linear dsDNA genome
  4. replicates in the CYTOPLASM
54
Q

where does poxvirus replicate in the cell?

A

the cytoplasm!!!

even though it’s a DNA virus, it replicates in the cytoplasm because it’s so huge it can afford to make its own machinery and doesn’t need the nucleus

they have virion-associated DNA dependent RNA polymerase that does the replicating for the virus, they don’t need the host RNA polymerase

55
Q

how many poxviruses infect humans? what are they?

A
  1. orthopoxviruses
  2. parapoxviruses
  3. yatapoxviruses
  4. molluscipoxvirus
56
Q

which viruses are orthopoxviruses?

A
  1. variola virus
  2. vaccinia virus
  3. cowpox virus
  4. monkeypox virus
57
Q

which virus causes smallpox?

A

variola virus

variola is an orthopoxvirus aka a poxvirus

58
Q

which viruses are parapoxviruses?

A
  1. Orf virus
  2. pseudocowpox
  3. bovine papular stomatitis virus
59
Q

which viruses are yatapoxviruses?

A
  1. tanapox virus
  2. yaba monkey tumor virus

both cause fever and localized single or multiple lesions

transmission from infected African primates

60
Q

which poxviruses are strictly human pathogens?

A
  1. variola virus (type of orthopoxvirus)

2. molluscipoxvirus

61
Q

what is the course of smallpox?

A

first you inhale air droplets or aerosols with initial infection of mouth, trachea and lungs but there’s no lesions or symptoms at this point

then the cells of the lungs/trachea get infected and the macrophages of the area will carry the virus to the lymph nodes which will cause the virus to infect the lymph nodes (˜day 4)

early replication in the lymph nodes produces flu like symptoms with a super high fever

then as the fever goes down, you get a huge rash in your mouth called an enanthem

then the enanthem goes away and it becomes an exanthem = a rash all over the outside of your body that’s super infectious; the rash will show up everywhere all at the same time

the infection is NOT contagious during the 1-2 weeks of incubation before the enanthem and exanthem

the rash then develops into pustules all ove

eventually the pustules dry up and scab over

then all the scabs fall off at the same time which is a problem because you’re basically losing all your skin at the same time and you die from infections..

62
Q

what does smallpox look like?

A

like little bubbles literally all over your entire body

63
Q

why is the smallpox vaccine so effective?

A
  1. humans are the only host - there’s no hidden population
  2. you’ll have lifelong immunity
  3. smallpox is a transient, not persistent infection
  4. vaccine is inexpensive
64
Q

what’s the risk with a smallpox vaccine?

A

it’s a live vaccine so they used to have really bad sores and stuff developing at the site of the smallpox vaccine

  1. encephalitis
  2. necrosis
  3. vaccine blisters spread all over the body
  4. accidental autoinnoculation
  5. death
65
Q

what is autoinoculation?

A

when the virus is spread from the fingertips to eyes or mouth

like if you scratch the vaccine site then touch your eyes….

66
Q

what is the vaccinia virus?

A

a type of orthopoxvirus

subspecies of buffalo pox virus

mainly in the indian subcontinent

67
Q

what is the cowpox virus?

A

a type of orthopoxvirus

rodent-borne and indigenous to rodents in europe/asia

68
Q

what is the monkeypox virus?

A

a type of orthopoxvirus

rodent-borne virus

reported in 9 west and central african rainforest countries

69
Q

what is the Orf virus?

A

a type of parapoxvirus

transmitted by infected sheep, goats, or wild artiodactyls

70
Q

what is the pseudocowpox virus?

A

a type of parapoxvirus

transmitted by infected dairy cows “milkers nodules”
Bovine papular stomatitis virus - transmitted by cattle

71
Q

what is bovine papular stomatitis virus?

A

a type of parapoxvirus

transmitted by cattle

72
Q

what are the two virus subfamilies associated with the parvovirus?

A
  1. aleutian mink disease

2. canine parvovirus

73
Q

what is the structure of parvoviruses?

A

2-3 capsid proteins

linear, single-stranded naked DNA

74
Q

what is AAV?

A

AAV = adeno-associated virus

it doesn’t cause any known disease in humans

its DNA integrates into a single site in human chromosome 19

it is used as an experimental gene therapy vector

75
Q

what are bocaviruses?

A

human bocaviruses are related to bovine (bo) and canine (ca) parvoviruses

76
Q

what are the clinical features of parvoviruses?

A
  1. seasonal infections = december - april

2. infections are respiratory diseases especially in kids

77
Q

what is B19?

A

the full name of parvovirus is parvovirus B19!!!

78
Q

what is the clinical presentation of B19?

A

it’s a parvovirus

presents as “slapped cheeks”

the mouth and nose area DON’T get red

79
Q

who gets infected with B19?

A

it is a global and common infectious pathogen in humans

common in kids but adults can also get it

80
Q

which type of antibody is directed against B19?

A

IgG

81
Q

how does B19 infect cells?

A

B19 virus infects cells expressing globoside (P-antigen) on their surface but it only replicates in proliferating cells such as RBC precursors

**B19 infects and kills the precursors to RBCs

temporary depression of erythropoiesis is likely a feature of all transient B19 infections, and usually not significant if no underlying hemolysis or erythroid compartment stress

transient aplastic crisis (TAC) results only when a shortened red-cell life span is coupled with failed erythropoiesis – TAC is self-limiting but the patient may be acutely ill and severly anemic

pure red cell aplasia and chronic anemia occur only when the patient cannot make neutralizing antibodies to clear B19 virus and stop loss of RBC precursors

82
Q

what is erythema infectiosum?

A

this is a low grade fever that lasts a week and then when the fever breaks the kid gets the slapped cheek rash on their face which then progresses to lacy reticular pattern that travels down the body

this is an innocuous rash illness with a mild fever

this happens during parvovirus B19 infection!

83
Q

what can B19 cause in adults?

A

occasionally, B19 is associated with an acute symmetric polyarthropathy that may mimic rheumatoid arthritis!

84
Q

when would parvovirus B19 cause TAC?

A

TAC = transient aplastic crisis

TAC can happen in patients infected with B19 if they have an underlying hemolytic disorder, such as sickle cell anemia, hereditary spherocytosis, enzymopathies or thalassemias, and acquired hemolytic anemias

when BM is depleted, the cell lines get depleted and the BM is only left with adipocytes – this is usually transient and the BM goes back to normal as the virus fades out

conditions of erythroid stress, such as hemorrhage and iron deficiency or bone marrow transplantation, can also be associated with TAC

85
Q

what happens if an immunocompromised person gets a B19 infection?

A

they can develop persistent B19 infections which cause pure red cell aplasia and chronic anemia

86
Q

what happens when a baby in utero is exposed to parvovirus?

A

fetal B19 infection causes death in utero, hydrops fetalis, or development of congenital anemia because of the immature immune status

if B19 is contracted during 1st 2 trimesters = hydrops fatalis = severe fetal anemia

87
Q

what are the 5 syndromes caused by parvovirus B19?

A
  1. Fifth disease
  2. anthropathy
  3. TAC
  4. persistent anemia
  5. hydrops fetalis and congenital anemia
88
Q

how can you diagnose B19?

A

children will have erythema infectiosum and exhibit a bright red rash on their cheeks (slapped cheek syndrome), lacy rash on trunk and limbs

you can also detect specific antibodies by ELISA or viral DNA by PCR

89
Q

how do you treat B19?

A

treatment of persistent B19 infection with immunoglobulin reduces viral load and results in a marked resolution of anemia

90
Q

what do you need for recovery from B19?

A

neutralizing antibodies

neutralizing antibodies bind to B19 virus and prevent the uncoating of virions – a single antibody will act to stabilize the virion so the capsid cannot open, trapping the genome

antibodies that bind to the virus may not neutralize virus infectivity so iff you are unlucky and make only non-neutralizing antibody, B19 will cause a fatal persistent infection unless immune immunoglobulin is administered

in such a patient, immunoglobulin must be given life-long; otherwise the virus will start replicating again

91
Q

what wart is associated with HPV 1-4?

A

verruca vulgaris = cutaneous common wart

transmission of warts is through physical contact

92
Q

how is parvovirus transmitted?

A

respiratory droplets

also it can be transmitted vertically from mother to child

93
Q

do poxviruses bud?

A

no, they make their own envelopes!!

94
Q

what are Guarniari bodies?

A

poxviruses replicate in the cytoplasm and they form inclusion bodies called Guarniari bodies!

these are diagnostic for poxviruses!!

95
Q

what does the core of a poxvirus look like?

A

dumbell

96
Q

what’s the difference between smallpox and chickenpox?

A

lesions are of the SAME age for smallpox (variola)

chickenpox will have a mixture of new ulcers, blisters and scabs (varicella)

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