Publication Date




Embargo Period


Degree Type


Degree Name

Doctor of Philosophy (PHD)


Microbiology and Immunology (Medicine)

Date of Defense


First Committee Member

Noula Shembade

Second Committee Member

Wasif N. Khan

Third Committee Member

Enrique A. Mesri

Fourth Committee Member

Savita Pahwa

Fifth Committee Member

Xiangxi Xu


Approximately 15% of human cancers worldwide, including leukemias and lymphomas, are caused by infection from oncogenic viruses, such as human T-cell lymphotropic virus 1 (HTLV-1) and Kaposi's sarcoma herpesvirus (KSHV). Oncogenes of these viruses, such as Tax of HTLV-1, and viral G-protein coupled receptor (vGPCR) and viral FLICE inhibitory protein (vFLIP) of KSHV, maintain persistent inflammation via activation of NF-kB, a family of transcription factors. NF-kB is normally transiently activated in response to TNF, IL-1, and bacteria or viral infections. However, under certain pathologic conditions, such as inflammation or tumorigenesis, it is chronically activated. Here we show host factor Cell Adhesion Molecule 1 (CADM1) expression is significantly upregulated in primary human PBMCs infected with HTLV-1 or KSHV viruses. Viral oncogenes Tax, vGPCR, and vFLIP usurp host factor CADM1 to maintain chronic activation of NF-kB. Tax, vGPCR, and vFLIP interact with the cytoplasmic tail of CADM1 to maintain chronic activation of NF-kB in infected cells. Furthermore, NF-kB activation by Tax and vFLIP is initiated in the plasma membrane lipid rafts of HTLV-1 and KSHV-infected cells, respectively. In addition, CADM1 is critical for the proliferation and survival of KSHV-associated Primary Effusion Lymphoma (PEL) cells. These results strongly suggest that CADM1 plays key roles in HTLV-1 and KSHV-mediated tumorigenesis and may lead to the development of novel therapies.


Oncogenic virus; NF-kB; oncogene; inflammation; HTLV-1; KSHV

Available for download on Monday, September 28, 2020