Doctor of Philosophy (PHD)
Human Genetics and Genomics (Medicine)
Date of Defense
First Committee Member
Second Committee Member
Third Committee Member
Fourth Committee Member
Fifth Committee Member
Human Immunodeficiency Virus (HIV) is a highly lethal lentivirus which is responsible for a tremendous amount of suffering and death in the United States and throughout the world. By attacking the host’s immune system, HIV leaves the infected individual susceptible to a wide variety of opportunistic infections. HIV, like all viruses, relies on host cell factors for successful infection, replication and release of progeny virus. Previously, a large-scale functional genomic screen identified over 230 novel factors whose silencing inhibited viral replication in cultured cells. A more detailed examination of these HIV-dependency factors (HDFs) showed a significant enrichment for factors involved in the trans-Golgi network (TGN), a pathway which had not been previously implicated in HIV replication. To examine the role that the TGN-HDFs play in the HIV-1 life cycle, cells were silenced for the various factors and submitted to biochemical and cell biological analyses. The Conserved Oligomeric Golgi (COG) complex is a heteromer complex that functions as a tethering factor in concert with the Rab-family GTPase (RAB1) and the t-SNARE syntaxin 5 to facilitate the recruitment, interaction and fusion of membranes from early or late endosomes to the TGN. Our results show that the targeted silencing of components of COG complex each impaired HIV-1 replication, as measured by intracellular p24 staining. These results suggested that the impairment in HIV-1 replication in these silenced cells occurred prior to gag translation. Analysis of the different forms of the HIV-1 genome showed that the defect in HIV-1 replication occurred prior to late RT product formation. This inhibition of HIV-1 is dependent on the HIV-1 envelope glycoprotein since viral particles pseudotyped with the vesicular stomatitis virus glycoprotein (VSVg) were unaffected. Utilizing recombinant virus bearing beta-lactamase-Vpr fusion protein, I showed that this inhibition occurred after viral fusion. In addition, this defect in HIV-1 replication repeated in several HIV-1 subtypes indicating a potential therapeutic target against broad viral spectrum.
HIV; COG complex; HIV-dependency factors
Liu, Sicen, "Characterization of Role of Conserved Oligmeric Golgi (COG) Complex in Early HIV Events" (2014). Open Access Dissertations. 1290.