16 - Lymphotrophic Herpesviruses Flashcards
What are characteristics of blood-borne herpesviruses? What are the different types?
- Replication and latency in cells of lymphoid and myeloid origin
- Persistent infection - balance between lytic and latent states
Human B-herpesviruses
Human Gamma-herpesvirus (oncogenic)
What viruses fall within the B-herpesvirus family? What about the Y-herpesvirus family? What type of cell does each infect?
B:
- Cytomegalovirus: Monocytes
- Human herpesvirus-6: T lymphocytes
Y:
- Epstein-Barr virus: plasma cells
- Kaposi’s Sarcoma virus: plasma cells
What is the appearance of Cytomegalovirus (CMV)? What else is this disease referred to as? Who gets it?
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
What does CMV cause in healthy individuals? In a fetus? Immunosupprsessed? Or those with a long-term persistant infection?
- Healthy adults: asymptomatic or mild mononucleosis
- Leading cause of congenital birth defects: mild-severe mental retardation, deafness, death (TORCH)
- Immunosuppression: symptomatic
- Persistent infection: atherosclerosis
What are structural charactierists of CMV?
dsDNA that encodes its own replication machinery
Icosahedral nucleocapsid, enveloped
Tegument and RNA
How is CMV transmitted?
- Contact with virus-containing secretions: semen, blood, sliva, tears, urine, feces, breast milk.
- Mucosal sites
- Transfusions, organ transplcant, transplacental
- Shedding with or without symptoms
How can you prevent CMV? Where does transmission most often occur?
Washing hands after changing dipers or wiping nose/drool; Avoid contact with saliva.
Transmission most often at daycares.
Describe the dissemination of CMV?
Poorly released from cell, slow replication cycle.
Lytic replication in epithelial, dendritic, fibroblasts, smooth muscle, endothelial, mø, and trophoblasts.
Describe the latent infection and frequency of reactivation of CMV?
Latent: CD34+ hematopoietic progenerator cells and monocytes.
Freq of reactivation is ~1 in 10,000 monocytes
What is the immune response to CMV? Which is the most important?
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
Can the immune response completely control CMV? Can re-infection by different CMV variants occur?
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.
What are the symptoms of CMV in healthy adults and children?
Mild/often unapparaent: fever, fatigue, sore throat, headahce (lasts 2-3 wks)
Subclinical hepatitis, lymphocytosis (increased # of lymphocytes), and lymphadenopathy.
Mononucleosis: heterophile antibody negative
How would you diagnose CMV?
Serology: AgG avidity (increased IgG binding)
Owl’s eye cells in urine or tissues
Cultured virus
Detection of viral DNA using PCR
What are three ways to treat CMV infection? What can be given in parallel with these? Why isn’t acyclovir very effective?
- Ganciclovir (IV) or valganciclovir (oral)
- Foscarnet (IV)
- Cidofovir (IV)
Anti-CMV IgG products given in parallel
Acyclovir not very effective becayse CMV doesn’t encode a thymidine kinase.
What is the function of ganciclovir (IV) and valganciclovir (oral) for treating CMV infection?
They are activated via phosphorylation by a viral kinase and inhibit viral DNA polymerase.
What is the function of foscarnet in treating CMV infection? What about Cidofovir?
Foscarnet inhibits the pyrophosphate binding site on viral DNA polymerase.
Cidofovir does not require phosphotylation and inhibits viral DNA polymerase.
How common is congenital CMV? Infection during which trimester has worse outcomes?
1:150 infected at birth; 1:750 have birth defects
1st trimester infection has worse outcomes.
What are symptoms at birth of congenital CMV?
Petechial lesions (54%)
Small birth size (47%)
Hepatosplenomegaly (40%), jaundice (38%)
Hemolytic anemia, pneumonia, intracranial calcifications, microcephaly.
What occurs with perinatal infection of CMV?
Infection at time of birth from cervical/vaginal secretions.
Usually no clinical signs.
Transmission via breatmilk can occur.
How would you diagnose/detect congenital CMV?
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.
Symptomatic CMV infected newborns are candidates for treatment with what? What are permanent symptoms that may occur?
Valganciclovir treatment
Permanent symptoms: hearing loss (25%), mild-severe mental retardation, musculoskeletal abnormalities, seizures, and septal defects.
What type of immunosuppressed people get CMV infections? What is the result? How is it monitored?
Life threatening for HIV and transplant patients.
Monitored by PCR/NAT or IgG and managed with antivirals
What does CMV infection cause in transplant patients? What is evaluated in these pts?
Pneumonia, fever, hepatitis, encephalitis, myelitis, colitis, uveitis, retinitis, and neuropathy.
CMV donor and recipient status evaluated.
What does CMV infection cause in HIV patients?
Retinitis (rare with HAART)
Fever, esophagitis, gastritis, colitis, hepatitis, pneumonia, peripheral neuropathy, and encephalitis.
