#18 Viral infection and Transplants Flashcards by Meghan May

Polyomaviruses
genome
enveloped

non enveloped
dsDNA
2 distinct transcript units

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origin of polyomaviruse has:

viral promoters and origin of DNA replication

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function of miRNA in polyomavirus

shuts of early gene expression

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The most potent oncoprotein in polyomavirus

Large T antigen

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J Domain:

DNAreplication

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binds and disrupts tumor suppressor proteins RB, p130, p107 promoting cell proliferation

LXCXE:

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Helicase in polyomavirus :

binds and disrupts

tumor suppressor protein p53

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binds and disrupts

tumor suppressor protein p53

helicase

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LXCXE:

binds and disrupts tumor suppressor proteins RB, p130, p107 promoting cell proliferation

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Genome replication by:

large T- antigen

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alter activity of cellular protein phosphatase

Small T antigen:

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Tropism Defined by

Host Cell Surface Gangliosides

our VP1

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First isolated (1971) from the urine of a renal transplant patient (BK

BK polyomavirus (BKPyV)

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Infection of BK polyomavirus

Benign in healthy individuals
Disease upon immunosuppression
Infection occurs at young age

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Mechanism of transmission for BK polyomavirus

respiratory,urino-oral, fecal-oral routes?

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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.

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Disease seen from BK polyomavirus

10% of Renal transplant-polyomavirus
associated nephropathy (PVAN)
0-25% of BMT-haemorrhagic cystitis (HC)

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10% of Renal transplant-polyomavirus
associated nephropathy (PVAN)
0-25% of BMT-haemorrhagic cystitis (HC)

diesase from BK polyomavirus

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BK polyomavirus has ___ serotypes

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Where does JC polyomavirus grow

Grows in human glial cells in culture, 5-HT2A serotonin receptor

How many serotypes does JC have

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

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