In the Spotlight…
Molecular Genetics and Microbiology
Graduate Student Gisselle Medina

Dissertation Research:

My dissertation research focuses on the assembly and release stages of retroviruses with the Rous sarcoma (RSV) and Human Immunodeficiency Virus Type-I (HIV-1) as the model systems. All retroviruses have in common three genes, gag, pol and env that specify their structural and enzymatic functions. The Gag protein encoded byin the gag gene is sufficient for the formation and release of virus-like particles (VLPs) from Gag- expressing cells. The release of these VLPs from the plasma membrane requires distinct regions within the Gag protein termed late assembly (L) domains. L domains are found at varying positions within the retroviral Gags and are functionally exchangeable. Therefore, a major approach to study these processes (assembly and release) is to study the Gag protein. Recent studies have shown that Gag can interact with cellular proteins that facilitate the egress of the virus mediated through the interaction interact with Gag through thewith L domains. Many of these cellular proteins (i.e.e.g. Tsg101 and Nedd4) participate in cellular processes such as endocytosis and multivesicular body (MVB) biogenesis. However, it is not clear how the virus exploits these proteins without being degraded during its trafficking through the endocytic pathway. It is possible that non-endocytic proteins might facilitate enable Gag to reach the plasma membrane and direct the release of the virus. This study in conjunction with previous publicationsMy current work, in conjunction with published results (Medina et al., 2005), will establish the important role and the molecular basis of the interconnected network of proteins that facilitates the trafficking and release of the functionally exchangeable L domains of HIV-1 and RSV-Gag.

The methods we are using to address this problem include mass spectrometry, siRNA, expression of Gag proteins in different cell lines, in vitro mutagenesis, purification and analysis of virus particles, fluorescence and electron microscopy. Understanding how retroviruses exploit the host cell to facilitate the budding process could provide novel therapeutic inhibitors for human pathogens such as HIV-1 and Ebola virus.

B.S., Biology, SUNY New Paltz
Advisor: Dr. Carol A. Carter

Recipient of the 2006 Abrahams Award for Outstanding Achievement by a Graduate Student, Graduate Program in Molecular Genetics and Microbiology

Publications:

Vana, M.L., Yang, Y., Chen, A., Medina, G., Carter, C., and Leis, J. (2004) Role of Nedd4 and ubiquitination of Rous sarcoma virus Gag in budding of virus-like particles from cells. J. Virol. 78: 13943-53.

Medina, G., Zhang, Y., Tang, Y. Gottwein, E., Vana, M.L., Bouamr, F., Leis, J., and Carter, C.A. (2005) The functionally exhangeable L domains in RSV and HIV-1 Gag direct particle release through pathways linked by Tsg101. Traffic 6: 880-94.