Understanding the mechanism of antiretroviral nucleoside analogs as inhibitors of Epstein-Barr virus lytic DNA replication

Epstein-Barr virus (EBV) is a human B-cell tropic double-stranded DNA y-herpesvirus. To date, there are no antiviral agents proven to be clinically effective in the treatment of EBV infection or EBV-associated diseases. In the experiments contained in this thesis, we define the ability of nucleoside/nucleotide analogs licensed for the treatment of HIV to inhibit EBV lytic DNA replication in vitro. Using an established system of EBV lytic DNA replication in HH514-16 cells induced with butyrate, we validate azidothymidine (AZT) as an inhibitor of EBV lytic DNA replication. We further demonstrate that several antiretroviral nucleoside/nucleotide analogs, including stavudine (d4T), abacavir (ABC), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), effectively inhibit EBV DNA replication.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2020

Author dc:creator

• Drosu, Natalia C.

Advisor dc:contributor.advisor

• David E. Housman and Elazer R. Edelman.

• Biology.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/128407

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/128407