Lymphotropic Herpesviruses Flashcards Preview

Immunology > Lymphotropic Herpesviruses > Flashcards

Flashcards in Lymphotropic Herpesviruses Deck (35):
1

Lytic:

Latent:

Lytic: virus production and cell lysis

Latent: Viral genome silent in cells

2

Replication and Latency

Cytomegalovirus:

Epstein-Barr virus and Kaposi's sarcoma virus:

Roseolovirus:

 

Cytomegalovirus: Macrophage

Epstein-Barr virus and Kaposi's sarcoma virus: Plasma cell

Roseolovirus: T-lymphocyte

3

Cytomegalovirus

  • Rate of seropositivity associated with _______ _____ and ____
  • Infected cells identified by:

  • Socio-economic condition; age
  • Owl eye; inclusion body

4

Cytomegalovirus disease

  • Asymptomatic in healthy adults
  • Leading cause of congenital birth defects
  • Symptomatic upon immunosuppression
  • Long term persistent infection associations
    • atherosclerosis
    • Immunosenescence
    • Neuroblastoma

5

TORCH

Congenital birth defects: TOxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex

6

Basic characteristics of CMV

  • 230 kbp double stranded DNA genome
    • Expresses >750 different proteins
    • Encodes its own DNA replication machinery
  • Icosahedral nucleocapsid
  • Tegument proteins and RNA
  • Envelope with glycoproteins

7

CMV lytic replication cycle

  1. Binding/penetration
  2. Entry
  3. Transcription
  4. DNA replication (24-48 hours)
  5. Encapsidation (48-72 hours)
  6. Envelopment/Release (72-96 hours)

8

Stages of gene expression

Immediate, early, late

9

What is the assembly compartment?

Proteins released from the nucleus into a compartment in the cytoplasm where virion assembly occurs

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10

Cytomegalovirus Transmission

  • Direct contact with virus-containing secretions
    • bodily liquids
  • Inoculation onto a mucosal site
  • Other routes
    • blood transfusion
    • organ transplants
    • transplacental transmission
  • Shedding with or without symptoms

11

Transmission most often occurs at _________

daycares

12

CMV dissemination

  • Cell associated
  • Slow replication cycle
  • Lytic replication
    • epithelial, dendritic, fibroblasts, smooth muscle...
  • Latent infection
    • CD34+ hematopoietic progenitor cells, monocytes

13

Frequency of CMV reactivation

1 in 10,000 of infected monocytes

14

Immune responses to CMV

Innate response:

Humoral response:

Cell-mediated immune response:

Innate response: Macrophage, interferon and NK cells control but are insufficient to clear

Humoral response: Does not clear, but may limit reinfection or reactivation

Cell-mediated immune response: Important cytotoxic T cells kill CMV infected cells up to 10% of all CD* T cells in the body may be directed against CMV

15

Common CMV viral antigens

gB, gH, pp65, pUL128-31

16

CMV symptoms in healthy adults and children

  • Usually mild disease but often unapparent
  • Fever, fatigue, sore throat, headache
  • Liver function abnormalities
  • Lymphocytosis
  • Lymphadenopathy
  • Mononucleosis

17

Diagnosis of CMV

  • Serology
  • Owl's eye cells in urine or other tissues
  • Culture virus from clinical material and detect with immunofluorescence
  • Detection of viral DNA using PCR/NAT

18

Serology of CMV

  • IgM testing is highly variable
  • IgG indicates recent or distant past infection
  • Serial testing of IgG negative to positive can define positive infection
  • IgG avidity increases with time and can distinguish between recent and past infection

19

Treatment of CMV infection

  • Ganciclovir - inhibits viral DNA polymerase
  • Foscarnet - Inhibits the pyrophosphate binding site on viral DNA polymerase
  • Cidofovir - Inhibit viral DNA polymerase
  • CMV does NOT encode thymidine kinase so Acyclovir is less effective

20

Congenital CMV

  • Only 14% of women have heard of CMV
  • Perinatal infections
    • infection at birth from cervical/vaginal secretions
    • Transmission via mother's milk
    • Usually no clinical signs

21

Symptoms of infection

At birth:

Permanent symptoms:

At birth:

  • Petechial lesions
  • Small size
  • Hepatosplenomegaly
  • Jaundice

Permanent symptoms:

  • Hearing loss
  • Vision loss
  • Mild to severe mental retardation

22

Diagnosis of Congenital CMV infection

  • Screening pregnant women for CMV remains controversial
  • Detection of virus in amniotic fluid is a definitive test
  • Newborns who are symptomatic are candidates for ganciclovir treatment

23

CMV infection in immunosuppressed

  • Life threatening
  • Transplant patients 
  • HIV patients (Retinitis)
  • Monitored by PCR/NAT or IgG and managed with antivirals

24

ß-Herpes virus: HHV-6B

Disease in children:

Replication

Detection:

Disease in children:

  • 90% of children > 2 years old are seropositive
  • High fever
  • Rash occurs in 10%

Replication: Replicates in CD4+ T cells

Detection: Using PCR/NAT or serology

25

Epstein-Barr Virus (HHV4)

Seropositivity:

Disease:

Seropositivity: >95% by early 20s worldwide

- Asymptomatic infection

Disease:

  • Infectious mononucleosis
  • Post Transplant Lymphoproliferative Disorder (PTLD)
  • Lymphomas (B, T and NK-cell)

26

Basic characteristics of EBV

  • 172 kbp dsDNA genome
  • Nucleocapsid, tegument, and envelop with glycoproteins
  • Encodes about 70 proteins including DNA replication machinery
  • Immediate, early , and late gene expression

27

Possible outcomes of EBV infection


  • Replicate in b cells or epithelial cells 



  • Latent infection in memory B cells 





  • Stimulate and immortalize B cells
     

28

EBV lytic replication cycle

  • Transmission by saliva and blood
  • Limited to epithelium of pharynx and B cells due to restricted cellular receptor expression
  • Reactivation of latently-infected activated B cells

29

EBV

Latency type I/II:

Latency III:

Latency type I/II:

  • Viral antigens in memory B cells
  • EBNA1 (Latency I and II)
  • LMP1 and LMP2A (Latency II)
  • RNA EBER 1&2
  • Can lead to Burkitt's, Hodgin lymphomas, nasopharyngeal carcinoma

Latency III:

  • Viral antigens made in proliferating B cells
  • EBNA 1, 2, 3A, 3B, 3C, LP
  • LMP 1, 2A, 2B
  • RNA EBER1&2
  • Infectious mononucleosis, PTLD

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30

Immune Response to EBV

Humoral Response:

Cell Mediated:

Disease:

Humoral Response:

  • Neutralizing antibody - no effect on virus shed

Cell Mediated:

  • CD8+ T lymphocytes and NK clls - lysis of EBV infected cells
  • Loss of T cell function results in B cell proliferative disease
  • Mononucleosis from rapid proliferation of atypical T cells (Downey cells)

Disease: Overactive immune response

31

EBV mediated infectious mononucleosis

Epidemiology:

  • Usually age puberty - 25 years
  • Primarily exposure to EBV
  • 30-40% develop disease/symptoms
  • Transmission by saliva
  • 5-20% of B cells infected with EBV in first week

32

Post Transplant Lymphoproliferative Disease (PTLD)

  • Immunosupressie therapy activated infection
  • Incidence 1-33% transplants depending on organ
  • Arises in donor B cells or reactivation in recipient
  • Prognosis is often poor 40-70% mortality

33

Diagnosis of EBV

  • Serology - assess antibody status against EBV antigens
  • EBV mononucleosis - test for heterophile antibodies by agglutination of animal red blood cells
    • Paul Bunnell test - sheep rbc
    • Monospot test - horse rbc
  • PTLD - fluorescent in situe hybridization; PCR

34

EBV-Associated Lymphoma

  • Burkitts lymphoma
  • Nasopharyngeal epithelial carcinoma
  • B cell lymphomas
    • Hodgkin and non-Hodgkin lymphomas
  • Immunosuppressed patients and transplant patients

35

Kaposi's Sarcoma Herpesvirus (HHV8)

  • 165 kbp dsDNA genome
  • 0-5% prevalent in North America and >50% in parts of Africa
  • Seropositiveity varies with geographic area and correlates with incidence of KS