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IAHI Block 3 > 16 - Lymphotrophic Herpesviruses > Flashcards

16 - Lymphotrophic Herpesviruses Flashcards

1
Q

What are characteristics of blood-borne herpesviruses? What are the different types?

A
  1. Replication and latency in cells of lymphoid and myeloid origin
  2. Persistent infection - balance between lytic and latent states

Human B-herpesviruses

Human Gamma-herpesvirus (oncogenic)

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2
Q

What viruses fall within the B-herpesvirus family? What about the Y-herpesvirus family? What type of cell does each infect?

A

B:

  • Cytomegalovirus: Monocytes
  • Human herpesvirus-6: T lymphocytes

Y:

  • Epstein-Barr virus: plasma cells
  • Kaposi’s Sarcoma virus: plasma cells
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3
Q

What is the appearance of Cytomegalovirus (CMV)? What else is this disease referred to as? Who gets it?

A

Cyto (cell) + megalo (large); referred to as cytomegalic inclusion body disease, CMV disease, or inclusion body disease.

Infected cells look like Owl’s eyes (inclusion boddies).

RAte of seropositivity associated with socio-economic condition and age - 40-80% in the US, >90% in developing countries

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4
Q

What does CMV cause in healthy individuals? In a fetus? Immunosupprsessed? Or those with a long-term persistant infection?

A
  1. Healthy adults: asymptomatic or mild mononucleosis
  2. Leading cause of congenital birth defects: mild-severe mental retardation, deafness, death (TORCH)
  3. Immunosuppression: symptomatic
  4. Persistent infection: atherosclerosis
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5
Q

What are structural charactierists of CMV?

A

dsDNA that encodes its own replication machinery

Icosahedral nucleocapsid, enveloped

Tegument and RNA

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6
Q

How is CMV transmitted?

A
  1. Contact with virus-containing secretions: semen, blood, sliva, tears, urine, feces, breast milk.
  2. Mucosal sites
  3. Transfusions, organ transplcant, transplacental
  4. Shedding with or without symptoms
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7
Q

How can you prevent CMV? Where does transmission most often occur?

A

Washing hands after changing dipers or wiping nose/drool; Avoid contact with saliva.

Transmission most often at daycares.

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8
Q

Describe the dissemination of CMV?

A

Poorly released from cell, slow replication cycle.

Lytic replication in epithelial, dendritic, fibroblasts, smooth muscle, endothelial, mø, and trophoblasts.

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9
Q

Describe the latent infection and frequency of reactivation of CMV?

A

Latent: CD34+ hematopoietic progenerator cells and monocytes.

Freq of reactivation is ~1 in 10,000 monocytes

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10
Q

What is the immune response to CMV? Which is the most important?

A

Innate response: insufficient to clear

Humoral: may limit reactivation but doesn’t clear; neutralizing Ab directed against surface proteins of virus

Cell-mediated: important!- cytotoxic T cells kill CMV infected cells and 10% of all CD8 T cells may be directed against CMV

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11
Q

Can the immune response completely control CMV? Can re-infection by different CMV variants occur?

A

No - immune system cannot completely control it.

Re-infection by different CMV strain occurs because of a high degree of viral genomic variability, even within the host.

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12
Q

What are the symptoms of CMV in healthy adults and children?

A

Mild/often unapparaent: fever, fatigue, sore throat, headahce (lasts 2-3 wks)

Subclinical hepatitis, lymphocytosis (increased # of lymphocytes), and lymphadenopathy.

Mononucleosis: heterophile antibody negative

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13
Q

How would you diagnose CMV?

A

Serology: AgG avidity (increased IgG binding)

Owl’s eye cells in urine or tissues

Cultured virus

Detection of viral DNA using PCR

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14
Q

What are three ways to treat CMV infection? What can be given in parallel with these? Why isn’t acyclovir very effective?

A
  1. Ganciclovir (IV) or valganciclovir (oral)
  2. Foscarnet (IV)
  3. Cidofovir (IV)

Anti-CMV IgG products given in parallel

Acyclovir not very effective becayse CMV doesn’t encode a thymidine kinase.

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15
Q

What is the function of ganciclovir (IV) and valganciclovir (oral) for treating CMV infection?

A

They are activated via phosphorylation by a viral kinase and inhibit viral DNA polymerase.

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16
Q

What is the function of foscarnet in treating CMV infection? What about Cidofovir?

A

Foscarnet inhibits the pyrophosphate binding site on viral DNA polymerase.

Cidofovir does not require phosphotylation and inhibits viral DNA polymerase.

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17
Q

How common is congenital CMV? Infection during which trimester has worse outcomes?

A

1:150 infected at birth; 1:750 have birth defects

1st trimester infection has worse outcomes.

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18
Q

What are symptoms at birth of congenital CMV?

A

Petechial lesions (54%)

Small birth size (47%)

Hepatosplenomegaly (40%), jaundice (38%)

Hemolytic anemia, pneumonia, intracranial calcifications, microcephaly.

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19
Q

What occurs with perinatal infection of CMV?

A

Infection at time of birth from cervical/vaginal secretions.

Usually no clinical signs.

Transmission via breatmilk can occur.

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20
Q

How would you diagnose/detect congenital CMV?

A

Screening mom remains controversial.

Detection of virus in amniotic fluid or in newborns urine/saliva:

  • PCR/NAT: 1 day
  • test newborn within first 2-3 wks.
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21
Q

Symptomatic CMV infected newborns are candidates for treatment with what? What are permanent symptoms that may occur?

A

Valganciclovir treatment

Permanent symptoms: hearing loss (25%), mild-severe mental retardation, musculoskeletal abnormalities, seizures, and septal defects.

22
Q

What type of immunosuppressed people get CMV infections? What is the result? How is it monitored?

A

Life threatening for HIV and transplant patients.

Monitored by PCR/NAT or IgG and managed with antivirals

23
Q

What does CMV infection cause in transplant patients? What is evaluated in these pts?

A

Pneumonia, fever, hepatitis, encephalitis, myelitis, colitis, uveitis, retinitis, and neuropathy.

CMV donor and recipient status evaluated.

24
Q

What does CMV infection cause in HIV patients?

A

Retinitis (rare with HAART)

Fever, esophagitis, gastritis, colitis, hepatitis, pneumonia, peripheral neuropathy, and encephalitis.

25
Q

What are characteristics of human herpes virus 6? What is this called?

A

Roseolavirus

dsDNA; replicates within CD4+ T cells.

Viral genome can integrate into host chromosome (only DNA virus to do so)

26
Q

What disease does human herpes virus 6 cause? Who does this occur in?

A

Roseola infantum/exanthema subitum - high fever ~4 days, malaise, and lymphadenopthy.

Rash (spares the head) and fever occur in 10% within 12-24 hours.

27
Q

When does Human herpes virus 6 reactivate? How do you detect HHV-6? How do you treat it?

A

Reactivated in stem cell transplant patients.

Detected using PCR/NAT or serology.

No treatments but can use anti-CMV drugs.

28
Q

What type of virus causes burkitt’s lymphoma? Who is seropositive for this virus?

A

Eptein-Barr virus (HHV-4), a gamma herpesvirus.

>95% seropositive by early 20s worldwide

90% EBV +ve (persitant lifelong infection) exhibit intermittent shedding without symptoms

29
Q

What results from infection with Epstein-Barr virus?

A

Often asymptomatic infections

Disease: infectious mononucleosis, post-transplant lymphoproliferative disorder (PTLD), and lymphomas (B, T, and NK cell)

30
Q

What is the structure of epstein-Barr virus?

A

dsDNA

Immediate, early, and late gene expression; encodes DNA replication machinery.

Nucleocapsid, tegument, and envelop with glycoproteins.

31
Q

What are the three possible outcomes of an EBV infection?

A
  1. replicate in epithelial and B cells
  2. Latent infection in mempory B cells
  3. Stimulate and immortilize B cells
32
Q

What EBV antigens are used for serology?

A

Lytic antigens: EMBA’s (EBV nuclear antigen), EA (early), MA (membrane), and VCA (viral capsid)

Latent antigens: EBNAs, LP (latent), LMPs (latent membrane proteins), and EBERs (EBV-encoded RNAs)

33
Q

How does EBV get transmitted and where does it infect?

A

Lytic replication cycle:

Transmission by saliva and blood; l

Infection limited to epithelium of pharynx and B cells due to restricted cellular receptor expression.

34
Q

What occurs in latency type III in EBV infection? What disease does this cause?

A

Viral antigens made in proliferating B cells

Specific EBNA’s, LMPs, and RNA’s made.

Lymphoproliferative disorders: infectious mononucleosis and post transplant lymphoproliferative disorder (PTLD)

35
Q

What occurs in latency type I/II in EBV infection? What disease does this cause?

A

Viral antigens in memory T cells (as opposed to proliferating T cells with type III).

Speficic antigens made.

Causes cancers: burkitt’s, hodgkin lymphomas, and nasopharyngeal carcinoma

36
Q

Describe the dissemination and latency phases of EBV?

A
  1. Infects epithelial cells, then Infects circulating B lymphocytes and cause them to hyperproliferate. This primary infection of EBV is associated with mononucleosis and latency phase III. Atypical downey cells also proliferate.
  2. Latency phase III can cause PTLD, while Lat II can cause progression to lymphomas.
  3. Lat 1 makes EBNA1 which tethers genome to host chromosome causing a lifelong persistant infection.
37
Q

What is the immune response to EBV?

A
  1. Humoral response: neutralizing antibodies used for antibodies dagnostics
  2. Cell-mediated: loss of T cell function results in B cell proliferative disease
38
Q

Mononucleosis results from what?

A

Rapid proliferation of atypical B cells infected with EBV - called downey cells.

39
Q

What effect does EBV have on the immune system?

A

Overactive immune response (infectious mononucleosis)

EBV-mediated B cell immortalization and lack of effective immune control (PTLD)

40
Q

At what age to people get EBV-mediated infectious mononucleosis? What symptoms occur with this disease? How do you treat it?

A

Puberty-25yrs (asymptomatic in yong children): primary exposure to EBV

5-20% of B cells infected within the 1st week - fever, malaise, lymphadenopathy, exudative pharynditis, splenomegaly (1-4 wks)

Polyclonal B cells produce “heterophile antibodies”

Self-limiting - treat symptoms

41
Q

What is Post Transplant Lymphoproliferative Disorder (PTLD)? When does it occur and when it the risk low?

A

An EBV-mediated B cell proliferative disease activated by immunosuppresive therapy.

Occurs within 1st year after transplant; low risk if graft contains donor T cells.

42
Q

What is the prognosis of post transplant lymphoproliferative disorder (PTLD)? What is a possible therapy?

A

Prognosis is poor: 40-70% mortality

Possible therapy is to reduce immunosuppression

43
Q

How do you diagnose primary EBV mononucleosis?

A

Test for heterophile antibodies by agglutination of animal RBCs:

  • Paul-bunnell test (sheep RBC)
  • Monospot test (horse RBC)
44
Q

How do you diagnose post transplant lymphoproliferative disorder (PTLD)?

A

Fluorescent in situ hybridization (FISH) to EBER RNA

NAT/PCR

45
Q

What is Burkitt’s lymphoma? Who is it found in? What causes this?

A

B cell lymphoma of the jaw/face; found in children in equatorial africa.

Associated with chromosomal translocation between chr 8/14

IgG promotor: myc proto-oncogene gets put in the promotor

46
Q

What is nasopharyngeal epithelial carcinoma? What geographical regions is it associated with?

A

EBV DNA in epithelial tumor cells

Chine, alaska, tunisia, and E. africa.

47
Q

What B cell lymphomas are associated with EBV?

A

Hodgkin and Non-hodgkin lymphomas

48
Q

What lymphomas are assocaited with EBV in immunocompromised pts?

A

Polyclonal lymphomas

Lymphocytis interstitial pneumonia

Hairy oral leukoplakia of the tongue (can’t scrape off)

49
Q

What is the structure of HHV-8? What type of virus is this? Where is it prevalent?

A

A gamma herpesvirus with dsDNA genome

0-5% prevalence in North America, and >50% in parts of Africa

50
Q

What diseases are associated with HHV-8?

A

Kaposi Sarcoma

Primary Effusion lymphoma

Multicentric Castleman disease

51
Q

How does HHV-8 replicate? How is the virus detected?

A

Replication in CD19+ peripheral B cells, endothelial cells, monocytes, keratinocytes, and epithelial cells.

Detection using PCR/NAT or serology.

IAHI Block 3 (18 decks)

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