Viral Infections in Transplant Patients Flashcards
Sources of Viral Infection in Transplantation
- Solid organ (SOT) and bone marrow (BMT) transplantation
- Infections may be present in recipient prior to transplant or acquired from donor
- Acquired via exposure in the post transplant setting
Polyomaviruses - characteristics
- Non-enveloped circular dsDNA virus
- 2 distinct transcriptional units
- Early and late region
- Agnoprotein: unknown function
- Origin contains viral promoters and origin of DNA replication
- microRNAs: late expression inhibiting early gene expression
Polyomaviruses
Early Region:
Late Region:
Early Region: Large T (LT), splice variants (LT’), and small T (ST) antigens
Late Region: Structural viral proteins, VP1-4
How many known polyomaviruses are there?
11
Large T-Antigen
J domain:
LXCXE:
NLS:
Helicase;
The most potent oncoprotein - genome replication
- J domain: DNA replication
- LXCXE: binds and disrupts tumor suppressor proteins RB, p130, p107
- NLS: nuclear localization signal
- Helicase: binds and disrupts tumor suppressor protein p53
Polyomavirus tropism define by host cell _____ _______
surface gangliosides
BK Polyomavirus
Infection:
Disease:
Infection:
- Benign in healthy individuals
- Disease upon immunosuppression
- Infection occurs at young age
Disease:
- 10% of Renal transplant-polyomavirus-associated nephropathy
- 10-25% of BMT-haemorrhagic cystitis (HC)
- Induces multiple types of tumors
JC Polyomavirus
Infection:
Disease:
Infection:
- Grows in human glial cells in culture
- disease upon immunosuppression
- Infection occurs at young age
Disease:
- Progressive Multifocal Leukoencephalopathy (PML)
- Induces multiple types of tumors when inoculated into experimental animals
Merkel Cell Polyomavirus (MCPyV)
- 80% of adults contain antibodies to virus
- Widely prevalent starting during childhood
- Merkel Cell Carcinoma (MCC) fast growing, painless, dome shaped
- Risk in immunocompromised (sun-exposed areas)
Phase I: Pre-Engraftment
Screenings (Donor and recipient):
- Hepatitis C
- HBV
- HIV
- Cytomegalovirus (CMV)
- Epstein Barr virus (EBV)
- Syphilis
Phase I: Pre-Engraftment
Infections due to immunosuppression
- Respiratory viruses
- Enteric viruses
- Human herpesvirus (6) reactivation
- Herpes simplex virus reactivation
Phase II: Post-Engraftment Days (30-100)
Risks:
Cytomegalovirus (CMV) reactivation
Adenovirus infection
Human Herpesvirus 6 reactivation
Community acquired respiratory viruses
Phase II: Post-Engfraftment (>100 days)
- Presence of chronic Graft Vs Host Disease (GVHD) requires continued immunosuppression of recipient
- Barrier protection of skin, mucous membranes and GI tract compromised with chronic GVHD
- Infection in this phase is generally localized to skin, Upper respiratory tract and lungs
- Viral infections are responsible for more than 40% of infections
Phase III: Late Phase
- VZV infections secondary to reactivation (median time = 5 months after transplantation)
- 85% develop herpes zoster; 15% chicken pox
- Increased risk of dissemination
Hemorrhagic cystitis can be caused by what viruses following pre-transplantation regimen (irradiation, cyclophosphamide or busulfan)?
Treatment?
BK, JC, and adenoviruses
Cidofovir (BK or adenovirus)
