M. Campbell, Ph.D.
My lab is focused on understanding the interactions occurring between retroviruses, such as Human Immunodeficiency Virus type-1 (HIV-1) and cellular restriction factors such as TRIM5a. TRIM5a has been shown to mediate a species specific block to infection, such that the TRIM5a protein from rhesus macaques potently inhibits HIV-1 infection, while HIV-1 is able to avoid restriction by TRIM5a protein present in the human population. My work seeks to better understand the molecular mechanism of restriction mediated by TRIM5a and other TRIM family proteins.
Much of the work in lab features the use of deconvolution microscopy to directly observe fluorescently labeled virions infecting target cells. We therefore hope to generate a better understanding of the biology of restriction by directly observing the interactions occurring between virions and restriction factors.
There are currently 3 projects in the lab. First, we have identified a region ofa that appears to mediate the multimerization of TRIM5a into discreet structures termed cytoplasmic bodies. We seek to understand the role this multimerization plays in restriction by examining TRIM5 mutants that have lost the ability to form these structures.. Second, we also are examining the regions of TRIM5 that mediate the binding and clearance of viral complexes during restriction by examining the kinetics of these events in the context of TRIM5a mutants with specific mutations in domains thought to be responsible for these activities. Third, we want to develop methods to fluorescently label other viruses during infection to observe the restriction of those viruses by TRIM5aproteins from other species, as well as recently reported antiviral activities possessed by other TRIM family members. Specifically, we want to develop the ability to fluorescently label murine leukemia virus particles, to observe the restriction of this virus by the human version of TRIM5a to better understand and differences in the restriction mediated by TRIM5a from human forms of the protein.
Sastri J, O’Connor C, Danielson C, McRaven M, Perez P, Diaz-Griffero F, Campbell EM. Identification of residues within the L@ region of TRIM5α that are required for retroviral restriction and cytoplasmic body localization. Virol, 2010, Manuscript accepted.
O'Connor C, Pertel T, Gray S, Robia S, Bakowska J, Luban J, Campbell EM. p62/Sequestosome1 associates with and sustains the expression of the retroviral restriction factor TRIM5α. J Virol. 2010, Jun; 84(12)5997-6006
Campbell EM, Hope TJ. Live cell imaging of the HIV-1 Lifecycle .Trends Microbiol. 2008 Dec; 16(12):580-7
Campbell EM, Perez O, Anderson JL, Hope TJ. Visualization of a proteasome independent intermediate during restriction of HIV-1 by rhesus TRIM5a, J Cell Bio, 2008 Feb 11;180(3):549-61
Campbell EM, Perez O, Melar M, Hope TJ. Labeling HIV-1 virions with two fluorescent proteins allows identification of virions that have productively entered the target cell. Virology. 2007 April 10;360:286-293 Nov 21
Campbell EM, Dodding MP, Yap MW, Wu X, Gallois-Montbrun S, Malim MH, Stoye JP, Hope TJ. Trim5a cytoplasmic bodies are highly dynamic structures. Mol Biol Cell. 2007, 18(6), 2102-2111
Wu X, Anderson JL, Campbell EM, Joseph AM, Hope TJ. Proteosome inhibitors uncouple rhesus TRIM5alpha restriction of HIV-1 reverse transcription and infection. PNAS. 2006 May9;103(19):7465-70