Parvo and Papova Viruses Flashcards
papova viruses include what 3 subfamilies?
- papilloma viruses
- polyoma viruses
- simian vacuolating viruses
polyoma genome:
- what type of RNA/DNA?
- where does it replicate?
- host range?
dsDNA covalently closed circular
replicates in the nucleus
narrow host range
- isolated from monkey kidney cultures
- cause tumors in hamsters, not humans
SV-40
-isolated in 1971 in fetal human brain cultures inoculated with extracts of brains from people with PML
JC virus
-isolated from urine of immunocompromised patient in 1971, 80% of population infected with this virus
BK virus
genomic organization of polyomavirus?
- structural proteins?
- regions?
- transcription?
- 3 structural proteins VP1,VP2, VP3
- dsDNA genome complexed with histones H2A, H2B, H3, H4
- early and late regions, early transcribed after genome enters nucleus, late expressed after DNA replication has begun
- transciption is bi-directional, early and late transcribed from opposite strands of DNA
early gene products of polyomavirus?
large t antigen, small t antigen
late gene products of polyomavirus?
VP1,2,3
- VP1 interacts with host cell receptor
- VP2 may interact with cell membrane
- DNA binding protein: autoregulation of early mRNA, DNA synthesis initiation
- helicase activity
- interaction with tumor suppressor genes (Rb and p53)
- induction of genomic instability
large T antigen
-dispensable for lytic cycle
-associates with regulatory and catalytic subunits of protein phosphatase 2A
-
small T antigen
T antigen binds _____ and releases the _____ transcription factors that induce expression of proteins such as cyclins A and E that promote cell cycle progression
pRB
E2F
t antigen also promotes transcription of p19ARF that acts to stabilize _______ through the protein _____ that controls turnover. inactivated upon t antigen binding, where it usually inhibits the cell cycle
p53
MDM2
JCV disease:
- enters through?
- persists in?
- persists indefinitely in?
- is the cause of what disease?
- enters through respiratory tract
- persists in B lymphocytes, also brain
- indefinitely in kidney
- cause of PML, a rare demyelinating disease of the CNS
JCV disease
- most often seen in what patient population?
- symptoms?
- target cell in the CNS?
- immunocompromised (AIDS, Hodgkins, TB, etc)
- symptoms are imparied speech and vision, mental deterioration, paralysis of limbs, blindness, sensory abnormalities, death within 3-6 months
- target is oligodendrocyte, nuclei 2-3X normal size filled with viral particles in dense crystalline arrays
BK multiplication in the urinary tract leads to?
hemorrhagic cystitis
BK virus persists in the ______ and is shed in the _______, most adults are seropositive for BKV
kidney, urine
- occurs in 1-10% of renal transplant patients
- reactivation of BK virus
- epithelial cells of tubules and collecting duct are infected, large nuclei, interstitial nephritis
- can result in renal transplant dysfunction and renal failure
polyomavirus associated nephropathy (PVAN)
- icosahedral, non enveloped dsDNA virus, covalently closed circular
- replication in the nucleus
- resist cell culture
papillomavirus
- high risk types of papillomavirus (16 and 18) lead to?
- low risk types of papillomavirus (6 and 11) lead to?
- cervical cancer, anogenital cancer
- cervical cell abnormalities that resolve spontaneously, genital warts (condyloma accuminatum)
papillomavirus genome:
- encodes for what proteins?
- capsid consists of?
- 8 proteins, early or late, early sufficient for transformation, late expressed in productively infected cells
- capsid consists of L1 and L2, DNA is associated with histones to form chromatin like complex
biologic characteristics of papillomavirus:
- high degree of species _______
- infects only ___________ of skin or mucosa
- most common clinical manifestation is ________
specificity-no examples of transmission to other species
surface squamous epithelia
warts (benign tumors)
papillomavirus replication cycle:
- initially infects the proliferating ________
- virus does not replicate in _______
- viral genome maintained at 20-100 copies in episomal state
- differentiation into keratinocytes triggers virus into ______ cycle
- basal cells
- basal cells
- lytic cycle
mechanisms of immune evasion by human papillomavirus?
- does not replicate in antigen presenting cells, lyse keratinocytes, or have a blood borne phase of replication –> decreased opportunity for immune system to detect HPV proteins and to mount immune response
- level of production of E6 and E7 in basal epithelium is low and restricted to cell nucleus: limits immune response
- HPV delays production of L1 and L2 capsid proteins until skin cells have terminally differentiated into squamous epithelial cells which are sloughed –> less accessible to immune cells
- infected keratinocytes may be relatively less susceptible to CTL lysis than other cell types
- anogenital warts
- 90% caused by HPV 6 and 11
- rarely become malignant
condylomata acuminata
- common wart
- hyperkeratotic papules
- HPV 2 and 4 most common
verucca vulgaris
potential outcomes of HPV infection?
cleared HPV infection, CIN1/2/3
integration of HPV genome into the host cell usually results in inactivation of ____
E2
papillomavirus early proteins:
- ____ and ____ are involved in genome replication and transcriptional control
- ______ protein has ATPase activity, helicase activity, and DNA binding activity
E1 and E2
E1
- transcriptional activator or repressor, repressed E6 and E7
- mutations disrupt transformation, replication, and transcriptional regulation
- not essential for replicatoin but makes viral DNA replication more efficient
E2 protein
E6 binds to and mediates the degradation of?
p53
E7 binds the ______ protein and displaces the _____ transcript, promoting progression through the cell cycle
Rb, E2f
