The Interaction of HIV with Cellular Protein Trafficking Pathways
Hi and welcome to my ePortfolio! My name is Justine and I'm a PhD student in the School of Life Sciences at the University of Warwick. I'm a Virologist funded by the MRC and part of the Infectious Agents group. I completed my BSc in Biological Sciences at Warwick in 2010, one of only a handful of students to achieve first class honours, and went straight into my PhD that year. I'm really interested in infectious diseases in both humans and animals, in particular HIV.
Supervisor: Emma Anderson ( http://www2.warwick.ac.uk/fac/sci/lifesci/people/eanderson ) Second Supervisor: David Evans (http://www2.warwick.ac.uk/fac/sci/lifesci/people/devans)
HIV-1 (Human Immunodeficiency Virus 1) is a lentivirus of the Retroviridae family that infects white blood cells of humans, ultimately causing the fatal disease AIDS (Acquired Immune Deficiency Syndrome). HIV utilises cellular replication machinery to produce viral RNA and proteins; these subunits that together make up new viral particles must first traffic to assembly sites on the plasma membrane of cells before new virions are produced. In order to do this, HIV hijacks cellular trafficking pathways that function to transport proteins to their required destinations. In particular, HIV makes use of the adaptor proteins AP-1, AP-2 and AP-3 which recruit and transport cargo in a clathrin-dependent manner. Depletion of AP-1 and AP-3 reduce HIV particle production, whereas depletion of AP-2 increases HIV particle production. We have shown that HIV infection relocalises AP-1 within HeLa cells. Depletion of AP-1 or -3 via siRNA treatment also causes HIV to be mislocated within the cell, away from intracellular budding sites, causing a delay in viral processing. We have also shown that HIV perturbs the trafficking of diphtheria toxin down the endosomal pathway which is AP-3 dependent, and causes slight sensitisation to ricin which traffics in an AP independent manner. We are currently using mutant viruses to determine the role of the viral proteins Gag and Nef in the perturbation of cellular trafficking molecules and pathways. This may provide some further insight into the detrimental effects of infection.
We have recently begun work on investigating HIV-2; much focus on the trafficking of HIV has focussed on HIV-1, and consequently little is known the mechanism of intracellular trafficking of HIV-2. Preliminary results have shown different dependences on the adaptor proteins between HIV-1 and -2, which is most likely due to the differing preferences in intracellular budding sites.
Long term HIV sufferers are also prone to HAD; HIV Associated Dementia, suffering various neurological problems such as anxiety, depression and memory loss. We are currently investigating the effects of HIV-1 on Astrocytes, a type of cell that makes up 90% of brain tissue and is shown to be infected in a large proportion of AIDS patients. I investigated the effects of HIV-1 on vesicle recycling via the use of fluorescence microscopy.
J dot E dot Alford at warwick dot ac dot uk
Infectious Agents RIG
School of Life Sciences
University of Warwick