Epstein-Barr virus and Cancer Flashcards
1
Q
What is Epstein-Barr virus (EBV)?
A
The fourth human herpesvirus (HHV4)
2
Q
How was EBV discovered?
A
- in 1958 Burkitt found lymphoma in children that as derived from viral particles discovered by Epstein and Barr
- It was similar structurally to other HHVs but has distinct biological activities
3
Q
What are the 3 subfamilies of HHV?
A
- alpha = HHV1/2, respiratory carcinomas
- beta = HHV5, Kaposi’s sarcoma
- gamma = EBV, Burkitt’s lymphoma/nasopharyngeal carcinoma
4
Q
What are some characteristics of EBV?
A
- member of the gamma subfamily of HHVs
- genome is a 172kb linear ds molecule that circulates in infected cells
- infects B cells and other certain epithelial cells
- efficiently immortalises resting B cells
5
Q
What are diseases associated with EBV?
A
- infectious mononucleosis (mono)
- Burkitt’s lymphoma
- nasopharyngeal carcinoma
- Hodgkin’s disease
- B cell lymphoma in immunocompromised hosts
6
Q
How does EBV infect B cells?
A
- infect via the viral glycoprotein gp350 which binds to the CD21 receptor found on B cells
- 2 regions of homology exist between the receptor and EBV which allows binding of the viral envelope and cell membrane
- EBV enters the B cell and the viral capsid dissolves to allow the viral genome to be transported to the nucleus
- can only infect B cells at certain times during their growth and maturation
7
Q
How does EBV infect epithelial cells?
A
- infect via viral protein BMRF-1 which binds to the cellular b1 integrins of the cell
- the viral protein gH/gL also binds with the integrins which triggers fusion of the viral envelope with the cell membrane
- EBV enters the B cell and the viral capsid dissolves to allow the viral genome to be transported to the nucleus
8
Q
How does EBV transmit?
A
- primary infection is usually asymptomatic in childhood
- virus is secreted in the saliva and is transmitted orally
- by the age of 40, almost ever everyone is infected
- could produce a lytic infection where <80 genes may be expressed
9
Q
How does EBV work latently?
A
- the initial lytic infection is followed by infected circulation of B cells
- results in persistent viral DNA in nucleus which establishes a latent infection
- latency depends on the differentiation stage of the cell
10
Q
How does EBV go from lytic to latent?
A
- lytic replication immediately follows viral entry (linear genome)
- once contact with CD21 receptor expressing B cells is made with EBV gp350, the virus enters the B cells and becomes latent (circular genome)
- the virus can then be reactivated back to lytic replication
11
Q
How can EBV lytic infection be treated?
A
- replication uses DNA polymerase
- Acyclovir can be phosphorylated by viral kinases that are only expressed in the lytic cycle
- it is converted into acyclovir triphosphate which can terminate viral DNA synthesis
12
Q
What can be seen from EBV infected cells placed in culture?
A
- EBV infected B cells give rise to a spontaneous out growth of EBV transformed cell line
- this is called lympoblastoid cell lines (LCL)
- LCLs can also be generated by infecting resting B cells with EBV which is useful for research
- every cell in LCLs express a limited set of viral gene products
13
Q
What latency type do EBV encoded genes belong in?
A
- Type l = EBNA1, EBER1/2
- Type ll = EBNA1, EBER1/2, LMP1/2
- Type lll = EBNA1/2/3, EBER1/2, LMP1/2
14
Q
Which latency types are found in different EBV infected cells?
A
- in epithelial cells, only ll is found
- in naive B cells, lll is found
- in GC infected cells, ll is found
15
Q
What is the function of EBV gene EBNA1?
A
- expressed in all EBV infected cells irrespective of latency type
- found in nucleus
- role in maintenance of genome through binding to origin of replication and allowing replication
- not recognised by cytotoxic T cells
- contains Gly-Ala repeat sequences to prevent degradation
- increases survival of infected B cells
- binds to p53 regulatory protein USP7 to lower p53 levels
- could be a target for future therapy
