#18 Viral infection and Transplants Flashcards
Polyomaviruses
genome
enveloped
non enveloped
dsDNA
2 distinct transcript units
origin of polyomaviruse has:
viral promoters and origin of DNA replication
function of miRNA in polyomavirus
shuts of early gene expression
The most potent oncoprotein in polyomavirus
Large T antigen
J Domain:
DNAreplication
binds and disrupts tumor suppressor proteins RB, p130, p107 promoting cell proliferation
LXCXE:
Helicase in polyomavirus :
binds and disrupts
tumor suppressor protein p53
binds and disrupts
tumor suppressor protein p53
helicase
LXCXE:
binds and disrupts tumor suppressor proteins RB, p130, p107 promoting cell proliferation
Genome replication by:
large T- antigen
alter activity of cellular protein phosphatase
Small T antigen:
Tropism Defined by
Host Cell Surface Gangliosides
our VP1
First isolated (1971) from the urine of a renal transplant patient (BK
BK polyomavirus (BKPyV)
Infection of BK polyomavirus
- Benign in healthy individuals
- Disease upon immunosuppression
- Infection occurs at young age
Mechanism of transmission for BK polyomavirus
respiratory,urino-oral, fecal-oral routes?
Where does the BK virus like to hang out once you get it?
• Likely persistent in proximal renal tubular cells, but capable of infecting lymphocytes and other cells.
Disease seen from BK polyomavirus
10% of Renal transplant-polyomavirus
associated nephropathy (PVAN)
0-25% of BMT-haemorrhagic cystitis (HC)
10% of Renal transplant-polyomavirus
associated nephropathy (PVAN)
0-25% of BMT-haemorrhagic cystitis (HC)
diesase from BK polyomavirus
BK polyomavirus has ___ serotypes
4
Where does JC polyomavirus grow
Grows in human glial cells in culture, 5-HT2A serotonin receptor
How many serotypes does JC have
1
when do we see disease from JC polyomoavirus
immunosuppreison at young age
Where does JCPyV persist
kidneys, lymphocytes, bone marrow
What disease does JCPyV cause
Progressive multifocalencepholopathy seen in 5-8% of AIDS encephalopathies
Progressive multifocalencepholopathy seen in 5-8% of AIDS encephalopathies
from JCPyV
Only PyV classified as a causative agent of a human malignancy
Merckel Cell polyomavirus
do we contain antiBs to meckel cell polyomavirus
yes, 80% adults to
Progression of Merkel Cell Carcinoma
fast growing, painless, dome shaped
Risk in immunocompromised, >60 yr old, often
occurs on sun-exposed areas
MCC
Clonal integration into host chromosome in most MCC and mutation of _____antigen in DDB
LgT
•_______ (oncoprotein) expression in ~97% of
MCC
LgT antigen
Phase I: Pre engraftment
Screen to identify potential infections that may put the patient at risk of death following the immunosuppression that precedes transplant
both donor and receipt
Key screenings are for
- Hepatitis C virus (HCV)
- Hepatitis B virus (HBV)
- Human immunodeficiency virus (HIV)
- Cytomegalovirus (CMV)
- Epstein-Barr virus (EBV)
- Syphilis
Pre-transplant chemotherapy and radiation and the post-transplant immune suppression: cyclosporine, tacrolimus put the patient at risk of infections
• Pre-engraftment infections due to :
immunosuppression
- Respiratory viruses
- Enteric viruses ‘
- Human herpesvirus 6 (HHV6) reactivation
- Herpes simplex virus (HSV) reactivation
pre-engraftment infections
Phase II: Post-Engraftment
Days 30-100
worry about:
• Cytomegalovirus (CMV) reactivation
• Adenovirus infection
• Human herpesvirus 6 (HHV6) reactivation
• Community-acquired respiratory viruses:
influenza/respiratory/humanmetapneum/picorna
Phase II: Post-Engraftment >100 days
presence of GVHD requires constant _______ during post transplant
GVHD
Chronic GVHD and it’s treatment are issues
ongoing cellular/humoral immunity defects in pts
Phase II:
Chronic GVHD compromises skin, mucous membranes and GI thus infections during Phase II are usulaly
in lungs, skin, URT
-
During Phase II, viral infections, especially secondary to VZV, are responsible for
more then 40% of infections
Late phase III:
see lots of______
VZV infections secondary to reactivation
usually 5 months after transplant
85% pts with reactivated VZV devo ____
15% devo ______
herpes zoster
chx pox
pts that devo ch pox have increased risk for
systemic infction like pnemonia, hepatitis
Hemorrhagic cystisis: from BK, JC and adenovirus occur:
Following irradiation, cyclophosphamide or busulfan in the pre-transplantation regimen, and prolonged aplasia after transplantation
Early development of Hemorrhagic cystisi associated with
high- dose cyclophosphamide before transplantation
Late-onset hemorrhagic cystitis (> day 15) from
BK, JC virus, or adenoviruses
TX for BK or adenovirus associated with hemorrhagic cystitis
Cidofovir successfully will treat BK or adenovirus–associated hemorrhagic cystitis.
Goals of devo of effective intervention therapies
more effective antivirals
virus specific vaccines
immune modulation
