Term
| T/F EBV and KSHV diseases are mostly associated with latency. |
|
Definition
| true: small subset of viral genes expressed |
|
|
Term
| What is the genome of EBV and KSHV? |
|
Definition
|
|
Term
| What's the size of the EBV genome? |
|
Definition
|
|
Term
| What's the size of the KSHV genome? |
|
Definition
|
|
Term
|
Definition
| B lymhpocytes and epithelial cells |
|
|
Term
| hat percent of humans are EBV+? |
|
Definition
|
|
Term
| What is the tropism of KSHV? |
|
Definition
| endothelial and epithelial cells (very small % in non-HIV+) |
|
|
Term
| How many proteins does the EBV genome encode? |
|
Definition
|
|
Term
| How many proteins does the KSHV genome encode? |
|
Definition
|
|
Term
| What is the structure of EBV and KSHV genome inside the host nucleus? |
|
Definition
|
|
Term
| For EBV, only __ of the 94 portiens are necessary for cell proliferation (similar pattern in KSHV). |
|
Definition
|
|
Term
| What are the entry receptors for EBV? |
|
Definition
| MHC class II and CD21 on B cells |
|
|
Term
| What are the entry receptors for KSHV? |
|
Definition
| DC-SIGN and integrin alpha V beta 3 |
|
|
Term
| What oral lesion is caused by EBV in AIDS patients? |
|
Definition
| oral hairy leukoplakia (epithelial hyperplasia) |
|
|
Term
| What are two colloquial names for infectious mononucleosis? |
|
Definition
| kissing disease or glandular fever |
|
|
Term
| What's the difference between acute and chronic mononucleosis? |
|
Definition
acute resolves in <3-4 months without intervention
chronic is rare and persists for more than 6 months |
|
|
Term
| How do you diagnose mononucleosis by looking at lymphocyte differential? |
|
Definition
| normally B cells are about 10-15% of lymphocytes but in Mononucleosis 50% are B cells |
|
|
Term
| What causes the heterophile IgM response? |
|
Definition
| EBV-induced differentiation of B-cells into proliferating blasts that secrete their preprogramed antibody |
|
|
Term
|
Definition
| heterophile IgM agglutinate sheep RBCs |
|
|
Term
| How do you diagnose mono? |
|
Definition
| bunnel test, IgM response against virus capsid antigen, IgG response against EBV nuclear proteins= both antibody responses are seen after diseaes resolution |
|
|
Term
| What is the tx for acute mono? |
|
Definition
| acetominophen (tx symptoms) |
|
|
Term
| What is the tx for chronic mono? |
|
Definition
| corticosteroids, esp prednisone (suppreses production of IL-1alpha by neutrophils which stimulates B-cell proliferation)--> reduces lymph node and tonsilar swelling |
|
|
Term
| Are anti-herpetics effective in treating mono? |
|
Definition
| clinical trial results: reduced cell-free viral load, no reduction in disease course or alleviation of symptoms (dz is caused by proliferation of latently infected b cells not viremia); possibly useful in severe chronic disease |
|
|
Term
| How do B cells proliferate? |
|
Definition
| CD40 on B to CD40L on CD4; MHCII to CD4. Starts NFKB and AP-1 signaling cascades in B cell. B cell activation and proliferation |
|
|
Term
| How do B cells become plasmablasts in EBV infection? |
|
Definition
notch on B cell binds to deltex on T cell, neutrophil or NK cell
Notch-dependent "suppressor of hairless" pathway that promotes differentiation to antibody-secreting blast. plasmablast normally undergo apoptosis when antigen disappears. |
|
|
Term
| What is the function/mechanism of LMP1? |
|
Definition
| activates NFKB and AP-1 pathways without a ligand (normally CD40 and CD40 L) |
|
|
Term
| What is the function/mechanism of EBNA2? |
|
Definition
| activates suppressor of hairless pathway without a ligand (notch + deltex) |
|
|
Term
| What is the function of EBNA 3 and EBNA1? |
|
Definition
| block apoptosis, so EBV+ cells don't die (have other functions as well) **most plasmablasts undergo apoptosis** |
|
|
Term
| How does EBV's EBNA-1 help evade the immune response by regulating replication? |
|
Definition
| restricts viral replication to once per cell cycle to prevent being recognized by immune cells |
|
|
Term
| How does EBNA-1 prevent viral antigens from being efficiently presented? |
|
Definition
| EBNA1 has long (~250aa) repeat of glycine and alanine that associates with the proteosome but can't be easily degraded. Therefore, other viral antigens aren't efficiently presented |
|
|
Term
| How do you go from EBV B cell proliferation to cancer? |
|
Definition
cell cycle checkpoints lost = immortalized cell with the capacity to proliferate but still responds to cues that limit proliferation
differentiation/apoptosis/response to DNA damage= transformed cells that proliferate in an uncontrolled manner leads to metastasis, etc. |
|
|
Term
| EBV was first isolated from... |
|
Definition
| Burkitt's lymphomas from children in sub-saharan africa |
|
|
Term
| What was the first human tumor virus to be identified? |
|
Definition
|
|
Term
| How often do EBV and burkitt's lymphoma correspond? |
|
Definition
| 100% of endemic burkitt's and >50% of sporadic burkit's lymphoma |
|
|
Term
| What is the classical histological finding of EBV/burkit's lymphoma? |
|
Definition
| small, noncleaved B cells in lymph nodes |
|
|
Term
| What are the symptoms of Burkit's lymphoma? |
|
Definition
| unexplained swollen lymph nodes that expand rapidly in size but are painless. Endemic BL often has a jaw bone or thyroid presentation. Sometimes endemic and almost always sporadic BL can have a unexplained rapidly expanding generally painless abdominal mass |
|
|
Term
| What are the molecular characteristics of BL? |
|
Definition
EBNA1 but no other EBV proteins present
chronosomal translocation that activates the c-myc protooncogene t(8:14) |
|
|
Term
| How many new lymphomas are there each year in the US? |
|
Definition
| approx 74,000 new lymphomas per year |
|
|
Term
| How many lymphoma-associated mortalities are there per year? |
|
Definition
|
|
Term
| What percent of lymphomas are EBV positive? |
|
Definition
|
|
Term
| What is the five-year survival rate of lymphomas? |
|
Definition
| 60-80% (state and metastasis dependent) |
|
|
Term
| T/F Lymphoma has a higher annual diagnosis and annual mortality than leukemia, cervical cancer, and melanoma. |
|
Definition
|
|
Term
| Is the 5 year survival rate better for lymphoma or leukemia? |
|
Definition
| lymphoma (60-80%) better than leukemia (50%) |
|
|
Term
| Kaposi's sarcoma and _____ were the earliest AIDS defining malignancy in 1985. |
|
Definition
|
|
Term
| T/F The increase in annual US lymphomas is largely due to EBV-positive lymphomas in AIDS. |
|
Definition
|
|
Term
| What are the AIDS associated lymhpomas? |
|
Definition
| CNS lymphomas, immunoblastic lymphomas, burkitt's lymphoma, primary effusion lymphoma, hodgkin's disease |
|
|
Term
| CNS lymphoma is an AIDS associated lymphoma if... |
|
Definition
|
|
Term
| Immunoblastic lymphoma is AIDS-associated if.. |
|
Definition
|
|
Term
| What percent of AIDS associated burkit's lymphoma is EBV positive? |
|
Definition
| 80% (only EBNA1, chromosomal translocation) |
|
|
Term
| Primary effusion lymphoma is AIDS associated if... |
|
Definition
| EBV/KSHV double positive; at least EBNA-1 |
|
|
Term
| What percent of AIDS associated Hodgkin's disease is EBV positive? |
|
Definition
|
|
Term
| What is the effect of HAART on lymphomas? |
|
Definition
| decreases the percent of EBV and KSHV positive lymphomas. PreHAART EBV positivity was 88%, KSHV was 6.5%. HAART era EBV positivity is 60% and KSHV positivity is 2.5% |
|
|
Term
| T/F HAART has caused the incidence of lymphoma to rise. |
|
Definition
| true, lymphoma incidence increases due to HAART dependent increased life-span |
|
|
Term
| How does EBV enhance CNS and immunoblastic lymphoma proliferation? |
|
Definition
provides proliferative signals (LMP1 and EBNA2)
provides anti-apoptotic signal (EBNA1 and EBNA3) |
|
|
Term
| How does EBV enhance Burkitt's lymphomas? |
|
Definition
| provides anti-apoptotic signals via EBNA1 |
|
|
Term
| What are three main KSHV genes that are similar to EBV genes? |
|
Definition
|
|
Term
| What is the function of K1? |
|
Definition
| activates NFKB, NFAT pathways to cause B-cell proliferation (like EBV's LMP1) |
|
|
Term
| What is the function of vFLIP? |
|
Definition
| blocks apoptosis (like EBNA1 and 3 of EBV) |
|
|
Term
| What is the function of LANA? |
|
Definition
| genome replication (like EBNA1 of EBV) |
|
|
Term
| What patient populations are susceptible to kaposi's sarcoma? |
|
Definition
indolent disease in elderly mediterranean men
aggressive disease in HIV+ men |
|
|
Term
| What is the appearance of kaposi's sarcoma? |
|
Definition
| bluish-black papular nodules seen on the skin but also elsewhere including the gastrointestinal and respiratory tract |
|
|
Term
| What cells are proliferating in Kaposi's sarcoma? |
|
Definition
| highly vascularized spindle cells |
|
|
Term
| What is the therapy for Kaposi's sarcoma in HIV+? |
|
Definition
| HAART, radiation, cyrosurgery, interferon alpha |
|
|
Term
| What is primary effusion lymphoma? |
|
Definition
| lymphoma of pericardium or pleural cavity. also called body cavity lymphoma. Very poor prognosis and highly resistant to therapy |
|
|
Term
| What % of primary effusion lymphomas are KSHV positive? KSHV/EBV double positive? |
|
Definition
|
|
Term
| What is lymphoma chemotherapy? |
|
Definition
| Cyclophosphamide, hydroxydaunorubicin, oncovin, (methotrexate), prednisone |
|
|
Term
| What is the function of cyclophosphamide? |
|
Definition
| damages DNA by akylation to block DNA replication |
|
|
Term
| What is the function of hydroxydaunorubicin? |
|
Definition
| intercalates into DNA, reduces gene expression, causes DNA damage |
|
|
Term
| What is the function of oncofin? |
|
Definition
| interferes with tubulin to block mitosis |
|
|
Term
| What is the function of methotrexate? |
|
Definition
| inhibits DHFR to reduce nucleotide biosynthesis |
|
|
Term
| What is the function of prednisone? |
|
Definition
| decrases IL-1alpha to reduce B cell proliferation |
|
|
Term
| Do EBV+ lymphomas respond to CHOP/CHOMP therapy? |
|
Definition
| although they are high-grade lymphomas they respond well except for PEL |
|
|
Term
| Which are more recalcitrant to therapy, reccurrent EBV+ lymphomas or EBV- lymphomas? why? |
|
Definition
EBV+
some EBV proteins (LMP1, EBNA1) promote mutagenesis |
|
|
Term
| What therapy is used for CHOMP resistant lymphomas? |
|
Definition
| rituximab (rituxan)= monoclonal antibody against CD20. More recently, autologous CTL therapy against EBV positive lymphoma cells is effective against some lymphomas |
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