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Immunology > Lymphotropic Herpesviruses > Flashcards

Lymphotropic Herpesviruses Flashcards

1
Q

Lytic:

Latent:

A

Lytic: virus production and cell lysis

Latent: Viral genome silent in cells

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2
Q

Replication and Latency

Cytomegalovirus:

Epstein-Barr virus and Kaposi’s sarcoma virus:

Roseolovirus:

A

Cytomegalovirus: Macrophage

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

Roseolovirus: T-lymphocyte

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3
Q

Cytomegalovirus

  • Rate of seropositivity associated with _______ _____ and ____
  • Infected cells identified by:
A
  • Socio-economic condition; age
  • Owl eye; inclusion body
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4
Q

Cytomegalovirus disease

A
  • Asymptomatic in healthy adults
  • Leading cause of congenital birth defects
  • Symptomatic upon immunosuppression
  • Long term persistent infection associations
    • atherosclerosis
    • Immunosenescence
    • Neuroblastoma
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5
Q

TORCH

A

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

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6
Q

Basic characteristics of CMV

A
  • 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
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7
Q

CMV lytic replication cycle

A
  1. Binding/penetration
  2. Entry
  3. Transcription
  4. DNA replication (24-48 hours)
  5. Encapsidation (48-72 hours)
  6. Envelopment/Release (72-96 hours)
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8
Q

Stages of gene expression

A

Immediate, early, late

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9
Q

What is the assembly compartment?

A

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

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10
Q

Cytomegalovirus Transmission

A
  • 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
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11
Q

Transmission most often occurs at _________

A

daycares

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12
Q

CMV dissemination

A
  • Cell associated
  • Slow replication cycle
  • Lytic replication
    • epithelial, dendritic, fibroblasts, smooth muscle…
  • Latent infection
    • CD34+ hematopoietic progenitor cells, monocytes
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13
Q

Frequency of CMV reactivation

A

1 in 10,000 of infected monocytes

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14
Q

Immune responses to CMV

Innate response:

Humoral response:

Cell-mediated immune response:

A

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

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15
Q

Common CMV viral antigens

A

gB, gH, pp65, pUL128-31

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16
Q

CMV symptoms in healthy adults and children

A
  • Usually mild disease but often unapparent
  • Fever, fatigue, sore throat, headache
  • Liver function abnormalities
  • Lymphocytosis
  • Lymphadenopathy
  • Mononucleosis
17
Q

Diagnosis of CMV

A
  • 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
Q

Serology of CMV

A
  • 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
Q

Treatment of CMV infection

A
  • 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
Q

Congenital CMV

A
  • 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
Q

Symptoms of infection

At birth:

Permanent symptoms:

A

At birth:

  • Petechial lesions
  • Small size
  • Hepatosplenomegaly
  • Jaundice

Permanent symptoms:

  • Hearing loss
  • Vision loss
  • Mild to severe mental retardation
22
Q

Diagnosis of Congenital CMV infection

A
  • 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
Q

CMV infection in immunosuppressed

A
  • Life threatening
  • Transplant patients
  • HIV patients (Retinitis)
  • Monitored by PCR/NAT or IgG and managed with antivirals
24
Q

ß-Herpes virus: HHV-6B

Disease in children:

Replication

Detection:

A

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
Q

Epstein-Barr Virus (HHV4)

Seropositivity:

Disease:

A

Seropositivity: >95% by early 20s worldwide

  • Asymptomatic infection

Disease:

  • Infectious mononucleosis
  • Post Transplant Lymphoproliferative Disorder (PTLD)
  • Lymphomas (B, T and NK-cell)
26
Q

Basic characteristics of EBV

A
  • 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
Q

Possible outcomes of EBV infection

A
  • Replicate in b cells or epithelial cells
  • Latent infection in memory B cells
  • Stimulate and immortalize B cells
28
Q

EBV lytic replication cycle

A
  • 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
Q

EBV

Latency type I/II:

Latency III:

A

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
30
Q

Immune Response to EBV

Humoral Response:

Cell Mediated:

Disease:

A

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
Q

EBV mediated infectious mononucleosis

Epidemiology:

A
  • 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
Q

Post Transplant Lymphoproliferative Disease (PTLD)

A
  • 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
Q

Diagnosis of EBV

A
  • 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
Q

EBV-Associated Lymphoma

A
  • Burkitts lymphoma
  • Nasopharyngeal epithelial carcinoma
  • B cell lymphomas
    • Hodgkin and non-Hodgkin lymphomas
  • Immunosuppressed patients and transplant patients
35
Q

Kaposi’s Sarcoma Herpesvirus (HHV8)

A
  • 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

Immunology (17 decks)

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