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Flashcards in Viral Infections in Transplant Patients Deck (18):
1

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

2

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

3

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

4

How many known polyomaviruses are there?

11

5

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

6

Polyomavirus tropism define by host cell _____ _______

surface gangliosides

7

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

8

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

9

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)

10

Phase I: Pre-Engraftment

Screenings (Donor and recipient):

  • Hepatitis C
  • HBV
  • HIV
  • Cytomegalovirus (CMV)
  • Epstein Barr virus (EBV)
  • Syphilis

11

Phase I: Pre-Engraftment

Infections due to immunosuppression

  • Respiratory viruses
  • Enteric viruses
  • Human herpesvirus (6) reactivation
  • Herpes simplex virus reactivation

12

Phase II: Post-Engraftment Days (30-100)

Risks:

Cytomegalovirus (CMV) reactivation

Adenovirus infection

Human Herpesvirus 6 reactivation

Community acquired respiratory viruses

13

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

14

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

15

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)

16

Development of Effective intervention therapies

More effective antivirals

Virus-specific vaccines

Immune modulation

17

MCW Phase 1 Intervention hypothesis:

  • The adoptive transfer of Cytotoxic T Lymphocytes against Ad, CMV, and EBV will be safe with regard to producing GVHD or other infusion related toxicities
  • Remove patient blood before transplant and immugenize against possible post operative infections

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