HUMAN T-CELL LEUKEMIA VIRUS TYPE 1-ENCODED PROTEIN HBZ INCREASES VIRAL INFECTION

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Erica Korleski (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Human T-lymphotropic virus type 1 (HTLV-1) is a complex retrovirus , infecting CD4+ T lymphocytes. About 10 million people worldwide are infected with HTLV-1. HTLV-1 has been linked to adult T-cell leukemia (ATL) , a disease characterized by proliferation and infiltration of leukemic T-cells into tissues and organs throughout the body. Transmission of HTLV-1 is strictly through cell-cell contact. However , the precise mechanism behind this cell-cell transmission is unknown. It has been shown that HTLV-1 infected cells form virological synapses (VS) by polarizing their microtubules and viral components upon contact with uninfected cells. Hence , HTLV-1 takes control of the T-cell polarization machinery to guide virions to cell contacts. Prior to formation of the VS , HTLV-1 virions are stored at the surface of the cell in a biofilm. This biofilm , composed of a carbohydrate-rich extracellular matrix , surrounds the cell and protects the virions from immune recognition as the VS forms. A characteristic of HTLV-1 infected T-cell lines , correlated with the infection process , is these cells form clusters with one another in culture. Interestingly , we observed that cells expressing a particular viral protein , HTLV-1 basic leucine zipper factor (HBZ) , spontaneously aggregate , suggesting HBZ is involved in the cell-cell infection process. We tested this hypothesis and found infection increased in cells expressing HBZ. Self-aggregation and cluster formation of these cells suggested involvement of cell adhesion molecules. HBZ , a nuclear protein , regulates the expression of some cellular genes. Therefore , we performed quantitative reverse transcriptase PCR to analyze the expression of several adhesion molecules that have been previously shown to be upregulated in HTLV-1 infected cells. Among the genes analyzed , we found that the amount of intercellular adhesion molecule 1 (ICAM-1) was elevated in all HBZ-expressing cells. Furthermore , we found that an ICAM-1 antibody blocks aggregation of HBZ-expressing cells , and HBZ activates transcription from the ICAM-1 promoter. ICAM-1 plays crucial role in formation of the VS during HTLV-1 transmission. Therefore , overexpression of ICAM-1 by HBZ and HBZ-mediated homotypic aggregation might be important for viral transmission. Our ongoing research involves investigating other cellular genes that have the potential to be regulated by HBZ and also be involved in the cell-cell infection process through VS or biofilm formation.

Additional Information

Publication

Thesis

Language: English

Date: 2017

Keywords

HTLV-1, HBZ, Nrp-1

Subjects

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