Lymphotropic Herpesviruses Flashcards
What do lymphotropic herpesviruses all have in common?
Name the herpesviruses that are lymphotropic.
They replicate and stay latent in lymphoid (rather than neuronal) tissue.
HHV-4 through HHV-8, this includes CMV, EBV, and KSHV.
Cytomegalovirus
What strain of human herpesvirus is it?
How widespread is it?
How is it transmitted?
What cell does it target?
Cytomegalovirus
HHV-5.
Many are seropositive–40-80% in the US.
Transmitted by seemingly every bodily fluid, as well as blood/organ transplant and transplacentally. Note: Can symptomatically shed for a month before symptoms occur.
Monocytes.
Cytomegalovirus
Describe its pathogenesis and the immune response to it.
Who is at highest risk?
What symptoms are seen in typical infections?
Cytomegalovirus
Following inoculation on a mucosal surface, it infects monocytes and may disseminate broadly. Innate and humoral responses limit but cannot clear virus. CTL response is critical.
Anyone associated with daycares (including the children).
Usually asymptomatic or flu-like. Sometimes liver function abnormalities, lymphocytosis, lymphadenopathy and “mononucleosis” (not true mononucleosis).
Cytomegalovirus
How is it diagnosed?
How is it treated?
Describe the course and severity of CMV infection in the immunosuppressed.
Cytomegalovirus
Same as with other herpesviruses. Note: Microscopy can reveal “Owl’s eyes” or inclusion bodies. IgG/IgM can reveal disease timing.
Ganciclovir/Valganciclovir, Foscarnet, Cidofovir. IgG? Don’t use acyclovir since there is no thymidine kinase to activate it.
Affects transplant recipients and HIV patients. Serious, can cause hepatitis, colitis, encephalitis, neuropathies. Retinitis in HIV patients.
What are the symptoms and outlook of congenital CMV?
How can it be screened for?
How can childhood CMV infection be avoided?
Not good. Petechiae, hepatosplenomegaly, jaundice, hemolytic anemia, and permanent effects like hearing/vision loss and retardation.
Examine amniotic fluid of pregnant women–culture, run PCR. Test newborns!
Maintain hygiene–wash hands and toys, don’t share utensils, and avoid mixing saliva with the child.
Roseolavirus
What strain of herpesvirus is it?
How widespread is it?
Describe its pathogenesis and symptoms.
Roseolavirus
HHV-6b.
90% of children 2 years or older are seropositive.
It replicates in CD4+ T-cells, and can integrate into the host chromosome for latent infection (not clear in what cells, though). Causes fever & rash without late sequelae. Can affect stem cell recipients.
Epstein-Barr Virus
What strain of human herpesvirus is it?
How widespread is it?
How is it transmitted?
What cell does it target?
Epstein-Barr Virus
HHV-4.
Most widespread of the herpesviruses (>95% seropositive by their 20s).
Blood, saliva.
B cells mainly, maybe other lymphocytes.
Epstein-Barr Virus
Distinguish between its lytic and latent lifestyles.
What illnesses are seen with different latent infections?
Epstein-Barr Virus
Lytic is typical, occurs in active B cells and epithelial cells. expresses antigens like EA/MA/VCA (capsids and membrane).
Latent occurs in memory B-cells (III occurs in proliferating B cells), expresses antigens like LP/LMP (latent).
Latency III causes infectious mononucleosis and PTLD. Type I/II causes Burkitt’s/Hodgkin’s lymphomas and nasopharyngeal carcinoma.
Infectious Mononucleosis
How is it transmitted?
Who does it affect? How common is it?
What are its symptoms?
What role does the immune system play?
Infectious Mononucleosis
By saliva, hence “kissing disease”.
Adolescents and young adults who have not yet been exposed to EBV.
Fever, malaise, lymphadenopathy, pharyngitis, and splenomegaly (stay away from contact sports!) for up to 4 weeks.
Symptoms are due to T-cell response. B-cells produce heterophilic antibodies (diagnostic)
Post Transplant Lymphoproliferative Disorder
Who does it affect?
Describe its pathogenesis.
What is its outlook and how is it treated?
Post Transplant Lymphoproliferative Disorder
Organ transplant recipients on immunosuppression.
Reactivation of EBV, from B cells in either host or donor tissue.
Grim outlook. Typical drugs are inadequate–reduce immunosuppression. Many experimental therapies (engineered CTLs, anti-CD20 Ig, anti-IL6).
Describe the lymphomas that are associated with EBV.
Where and in whom do they affect?
Burkitt’s lymphoma (of jaw and face, in Africa), Nasopharyngeal epithelial carcinoma (in China, Alaska, Africa), Hodgkin’s and non-hodgkin’s lymphomas.
Often affect immunosuppressed and/or transplant patients. Note that Burkitt’s is associated with a chr 8-14 translocation.
How is Epstein-Barr virus usually diagnosed?
How about specifically infectious mono and PTLD?
What is the purpose of the EBNA1 antigen? When is it seen?
Serology for EBV antigens.
Mononucleosis: Agglutination tests for heterophile antibodies (Paul-Bunnell/Monospot).
PTLD: Fluorescent hybridization, NAT/PCR.
Tethers genome to host chromosome (latency I only).
Kaposi’s Sarcoma Herpesvirus
What strain of human herpesvirus is it?
How widespread is it?
What cell does it target?
What illness does it cause?
Kaposi’s Sarcoma Herpesvirus
HHV-8.
Not very widespread (0-5% prevalence in N. America)
B-cells. (plus endothelium, epithelium, monocytes, keratinocytes)
Kaposi’s Sarcoma, primary effusion lymphoma (PEL), multicentric castleman disease (MCD).
