CMV, EBV, & KSHV Flashcards
EBV, CMV and KSHV are all?
Herpes viruses.
What is is the Genomic structure of KSHV, CMV, and EBV?
Double Stranded DNA.
What is the structure of these viruses?
Each has an icosahedral core surrounded by a lipoprotein envelope
Where does replication of these viruses take place?
The genome is replicated and viruses assembled in the nucleus in the nucleus
What type of infections do these bugs produce?
Self-limiting infections
What are some of the possible complications from these bugs?
Life threatening infections or cancers can occur especially in immuno-compromised patients
What kind of replication do herpes viruses undergo?
Lytic replication in a variety of cell types.
What is important about the primary infection of these herpes viruses?
The primary infection is usually asymptomatic
How do the viruses invade a host cell?
Attachment and penetration happens via virus glycoprotein-mediated fusion of envelope and plasma membrane
How does the released nucleocapsid migrate to the nuclear envelope of the host cell?
Via microtubules
What are the (IE) Immediate Early genes?
Virus specific transcription factors.
What is the function of the Immediate early genes?
- Use host RNA Polymerase II
2. STimulate transcription at virus early promoters
What are early genes?
Genes expressed after IE genes that encode many nonstructural proteins and enzymes.
What is the function of the early genes?
- The generate DNA replication machinery including viral DNA polymerase
- Generate Thymidine kinase (tk) which phosphorylates a variety of nucleotides besides thymidine
- Encode many nonstructural proteins
What are the functions of late genes?
- Encode structural proteins (capsids & Glycoproteins)
What is the cause of syncytia formation?
Viral encoded glycoproteins
Where does virus assembly occur?
In the nucleus, nucleocapsids bud first into the perinuclear space
As an alternative to lytic infection what do all herpes viruses undergo?
Latency.
What happens to Herpes viruses during latency?
Entire viral genome is maintained extrachromosomally in the host but no virus particles are produced.
What are the three stages of latency?
- Establishment
- Maintenance
- Reactivation
Under what circumstances does reactivation occur?
- Lapse in immunity (AIDS=KSHV)
- Stress
- Sunlight
- Menstration
What are the Betaherpesvirnae?
- CMV
- HHV-6
- HHV-7
What are the Gammaherpesvirinae?
- EBV
2. HHV-8
How are the Betaherpesvirnae and Gammaherpesvirinae different from Alphaherpesvirinae?
More isidious (less aggressive)
Is CMV highly contagious?
No
What is a huge determining factor in the age at which one may be infected with CMV?
Socioeconomic status. (THE LOWER THE STATUS THE EARLY ONE TENDS TO BE INFECTED)
Where is CMV usually found?
Saliva, urine, breast milk, semen, cervical secretions,blood, and transplanted organs
Who are the most at risk populations?
Neonates, Gay men, day care workers, pregnant workers, immunocompromised patients
How is infection of CMV spread?
Through direct contact with secretions, NOT BY AEROSOL
Where does primary replication of CMV take place?
Epithelial cells followed by spread to lymphoid tissue
What cells does CMV latently infect?
B-cells, T-cells, monocytes, and lymphocytes.
What is a common characteristic of CMV infected cells?
CMV causes Large puffed up cells
What are the symptoms of neonatal in utero infections by CMV?
Usually asymptomatic but can result in retardation and deafness
What are the symptoms of adult infection?
Mostly asymptomatic but mononucleosis accompanied by fever can occur
What subset of patients are particular at risk?
Immunocompromised
What do most organ transplant patients get?
CMV infection with pneumonitis representing the most life threatening aspect
What are the 2 ways in which organ transplants lead to CMV infection?
- CMV from donor
2. Reactivation of CMV in recipient
What is a promising prophylactic regiment for organ transplant in relation to CMV?
1.ANti CMV Ig + Ganciclovir
What perticular complications from CMV is seen mostly in AIDS patients?
Primarily Retinitis but also colitis and pneumonitis.
How is a diagnosis of CMV made?
- ELISA or PCR detection
2. Shell vial assay uses immunofluorescence to detect an immediate early protein after 24H of cell culture infection
What is the treatment for CMV
Ganciclovir and the prodrug Valaganciclovir
What is Ganciclovir?
A guanosine analog similar to acyclovir
What drug is used in Ganciclovir resistant infections?
Foscarnet.
Is there a vaccine against CMV?
NO
What else is Foscarnet used to treat in relation to CMV?
Retinitis in AIDS patients
What is the predominant factor determining age of infection by EBV?
Socioeconomic status
What is the usually outcome of EBV infection in adolescence and early adulthood?
Infectious Mononucleosis
What percentage of the adult population contains the antibody to EBV?
90-95%
What can else can EBV cause in immunocompromised patients?
Oral Hairy LEUKOPLAKIA
What is OHL?
OHL usually develops when CD4 counts are <400 and is characterized by white hairlike projections arising from the side of the tongue (differentiated from Candidal thrush because OHL will not rub off with a tongue blade)
What disease is seen in transplant patients infected with EBV?
Posttransplant lymphoproliferative disease (PTLD)
What two Neoplasias are associated with EBV?
Burkitt’s lymphoma, Nasopharyngeal carcinoma
What is the primary way that EBV is spread?
Sucking faces (kissing saliva)
What is the incubation period for EBV?
4 to 7 weeks
Where does the initial viral replication take place in EBV infection?
Oropharyngeal epithelium
Where is the secondary site of infecttion in EBV?
Lymphoctes, spleen, then Liver
Where does EBV remain latent?
B-cells and throat epithelium
What occurs for many weeks during EBV infection?
Oral shedding
What are the symptoms of EBV infection?
1.Most infections are asymptomatic
What are the symptoms of Infectious Mononucleosis?
- Sore Throat
- Fever
- malaise
- lymphadenopathy
How does one arrive at a diagnosis of Infectious mononucleosis?
1.At least 50% atypical large lymphocytes with lobulated nuclei
What are these large lymphocytes?
T-Cells responding to the infection, NOT INFECTED B_CELLS
What are the antigenic markers for EBV?
- EBNA-EBV nuclear antigens arise early in primary infection
- Conversion to anti-EBNA IgG indicates resolution of primary infection - VCA - Viral capsid antigen
- Anti-VCA IgM indicates primary infection
- Anti-VCA IgG without anti-EBNA IgG indicates primary infection
- Anti-VCA IgG without anti-EBNA IgG indicates past infection - EA-early antigen is detected in cells that do not produce virus
What is the most commonly used tool to confirm a diagnosis of EBV infectious mononucleosis?
Test for heterophile antibodies (Monospot test)
- These antibodies agglutinate sheep red blood cells
- Not present in all patients, origin not understood
- Distinguishes EBV mono from CMV mono
What is the treatment for EBV Mono?
Supportive care
With hold athletes due to possible inflammation of the spleen
What is the treatment for Oral leukoplakia?
Acyclovir
What is PTLD?
Uncontrolled proliferation of B-Cells due to their transformation by EBV and the absence of CTLs to control them
What patients are at highest risk?
Highest risk is in seronegative transplant recipents in the first year
What is the treatment for PTLD?
Stop Immunosuppression
- but monitor closely for rejection
- Acylovir not helpful because the virus is latent and not reproducing
What is Burkitt’s Lymphoma?
Neoplasm of B-Cells that affects bones of the Jaw
-endemic in central Africa and New Guinea
What are the three factors associated with Burkitt’s?
- Early EBV infection leading to latency
- Activation of C-MYC
- Malaria
What is the cure rate with early detection of Burkitt’s?
80%
What is Nasopharyngeal carcinoma?
- Neoplasm of epithelial cells
- Associated with EBV world wide
- High frequency in Southern China-High salt diet cofactor
What is the initial presentation of Nasopharyngeal carcinoma?
Painless lump in neck
What is the survival rate for Nasopharyngeal carcinoma
At best 60% survive past 10 years
How is HHV-8 related Karposi’s sarcoma?
It is neccesary but not sufficient
Where does the latent virus reside in humans?
B-cell and endothelial cell latency tropism
Where do KS tumors occur?
In the lining of the lymphatic system
What happens to the lymphatic channels?
Fill with Bloodcells hence the bluish, bruised appearance of lesions
In what populations is KS classically seen?
Mediterranean and Sub-saharan african (Not STD in these cases)
What sub-population of patients in the US is KS most seen in?
AIDS patients
How is the virus transmitted?
Sexually but virus not present in semen or vaginal secretions but present in Saliva
What is the incubation period for KS?
10 years
When is KS life threatening
If the patient is immunocompromised
What must accompany infection for disease to be symptomatic
Loss of the immune system
What is the treatment in AIDS patients?
Resection and chemotherapy against the tumor
What 2 other B-Cell abnormalities is HHV-8 linked to?
- Primary effusion lymphoma
2. Castleman’s disease
What is Primary effusion Lymphoma?
- Non Hodgkin’s B-cell lymphoma
- Commonly found in body cavities
- mean survival time is 2-6 months
- KSHV found in virtually all tumors of HIV + patients
What is Catleman’s disease?
- Lymph node tumors, not strictly a cancer
2. KSHV found in essentially all tumors of HIV + patients