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
What are 3 ways HPV is transmitted?
Most HPV infections are __ (transient/persistent)
Sexually
Transplacentally
Oral infections (less common)
Most HPV infections are transient
What are the sexual and non sexual risk factors for HPV infection?
Sexual risk factors
For women: Lifetime sex partners, early sexual debut, male partner sexual behavior/circumcision
For men: Lifetime number of sex partners; being uncircumcised
Nonsexual risk factors
In women – smoking and oral contraceptive use
In both: young age
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**
What kind of tissues does HPV tend to infect?
Tissue specific: like squamous epithelium
Under control of host transcriptional machinery, but can also influence host machinery and induce cell differentiation
HPV mainly affects the __ layer of the squamous epithelium and it gets there thru ___
HPV targets basal layer and it reaches that layer thru microabrasions/trauma
Describe the pathogenesis of HPV (so after the trauma, the virus reaches the basal layer and then what happens?)
Proteoglycans on surface of basal layer cells are exposed, the virus (L1 protein) binds to those proteoglycans and enters into the cell via endocytosis. The L2 protein forms a complex with dna and reconfigures into an episome
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)
