Human Papillomavirus and Polyomavirus Flashcards
Describe the structure of papilloma and polyomavirus
Non enveloped, icosahedral capsid
DS circular dna, assembly in NUCLEUS
Name the 2 polyomaviruses that cause disease in humans
JC virus and BK virus
(jC - junk cerebrum and bad kidney)
During which age range does the seroprevalence of JC and BK polyoma viruses peak?
The most likely mode of polyoma virus transmission is ___
Between 5-9 yoa
Respiratory
The polyoma virus genome encodes early and late mRNA. __ encodes non structural proteins, and ___ encodes structural proteins
Early – non structural proteins, like when you’re born, you’re still kinda wimpy and don’t really have much structure; large T antigen inactivates p53 (anti-tumor protein) and retinoblastoma protein (Rb)
Late – structural proteins VP1, 2 and 3
**note that there’s also non-coding regions**
Primary infection with polyoma virus is usually ___. Clinical disease almost always in what group of people?
JC virus causes ___ (which is almost an infectious mimic of multiple sclerosis)
Primary infection with polyoma virus is usually asymptomatic. Clinical disease almost always in immunosuppressed folks.
JC virus causes progressive multifocal leukoencephalopathy (which is almost an infectious mimic of multiple sclerosis)
**remember, JC = junk cerebrum**
BK virus causes polyomavirus-associated nephropathy which occurs in what group of patients, and ___ which happens in stem cell transplant patients
BK virus causes polyomavirus-associated nephropathy which occurs mostly in solid organ transplant patients (renal transplant), causes ureteral stenosis, and hemorrhagic cystitis which happens in stem cell transplant patients
**remember BK = bad kidney**
Fill in the blanks (JC and BK cycle)
JC virus infects oligodendrocytes and astrocytes leading to what type of infection?
Describe the symptoms of PML
What populations of people get affected by this virus?
JCV infects oligodendrocytes, astrocytes >> lytic infection, myelin destruction
Symptoms: think asymmetric movement problems - gait imbalance, limb paresis, dyscoordination (also vision and cognitive dysfunctions)
Populations affected: immunosuppressed (HIV mostly but also cancer pts, solid organ transplant pts, mAb therapy)
Bonus question: what is the CD4 count at which HV pts are at risk for PML due to JC virus?
less than 200
Describe the features of PML in the brain imaging below? How else can you dx PML?
Dx: imaging
Hypointense on T1 weighted imaging, hyperintense in T2, does NOT enhance, likes periventricular areas, not so much subcortical
CSF evaluation: isolate virus from CSF
What apoptosis related protein is upregulated in PML and a new mAb against it has shown potential for therapeutic improvement?
Programmed cell death protein 1 (PD-1): negative immune regulator
Pembrolizumab: PD-1 blockade
Who virus this is?
Human papillomavirus
HPV causes multiple syndromes. Name 3
Warts (mucosal or cutaneous)
Recurrent respiratory papillomatosis
Cancer
HPV causes cervical, __, oropharyngeal and ___ cancer
Cervical cancer
Anal cancer
Oropharyngeal cancer
Vulvar, vaginal, penile cancer
(besides oropharyngeal, HPV causes cancer of the genitourinary tract for mainly women, and men - penile)
The main cervical cancer causing HPV types are __ and __ (both pretty awkward ages; how old you and Nadine were when you moved here)
HPV 16
HPV 18
Describe the structure of papillomavirus
Non enveloped, icosahedral
What do the early and late genes code for in Papilloma virus?
Early genes code for non structural proteins
Late genes code for L1 and L2 proteins which play an important role?
**see image below**
Describe what’s happening here
**note that the virus is pretty much untouched by the immune system**
Basically the virus infects the basal layer cells, and move up a layer (leaving one behind to keep the progeny going)
Once in the suprabasal layer, the virus basically turns on the early genes required for cell proliferation and that causes the rapid multiplication of cells in the suprabasal layer >> hence forming warts
As we move up the layers, then the virus turns on the genes for the genome amplification proteins L1 and L2. The virus assembles in the granular layer then are fully formed in the cornified layer. The viral particles shed with the dead skin
What happens when HPV is integrated into the host genome?
Viral integration: the HPV episome dna integrates into the host genome (doesn’t happen all the time) >> unregulated production of E6 and E7 (E2 gets lost, and that one downregulates E6 ad E7)
What are the functions of E6 and E7 in HPV?
see image below
**basically E6 is a like a car, right. you’re driving down the highway and you runover that nigga p53. Then cops coming for you so you induce telomerase i.e. speed up and increase your polarity by turning the radio on to the PZD channel
E7 steals rubies (as in Rbs) and degrades them then sells them so he can control the drug cycle (cell cycle)
Which HPV serotypes cause anogenital warts?
What’s the lesion that you find when you biopsy these things?
HPV 6 and 11 cause anogenital warts (so if you’re 11 + 6 = 17 and you start sexing at 17, you gon get anogenital warts)
CIN-1 : like these hoe-ish kids are commiting CINs by all this promiscuity
T/F: CIN1 is a precursor for cancer
Nope. It isn’t. See below
How does recurrent respiratory papillomatosis manifest?
**see below**
What is the significance of CIN1 and 2 in cervical cancer caused by HPV?
Difference between CIN 2 and 3 depends on how much of the epithelium is taken up by the dysplasia
**also, see below for actual answer**
Where in the head and neck region does HPV go?
HPV affects the base of the tongue in head and neck cancer
How do you process a sample for cervical/anal cancer screening?
see below
