The role of cellular and, in particular, actin cytoskeletal factors in HIV-1 replication events in primary cells.
HIV-1 subverts the immune system during pathogenic infection, resulting in a gradual depletion of CD4 T cells and a loss of immune functionality that ultimately results in Acquired Immunodeficiency Syndrome (AIDS). In line with this, HIV-1 has evolved a complex network of interactions with cellular proteins by which this coercion occurs. Our research, as of the Yoder et al 2008 publication listed below, has predominantly focused on a particular subset of cellular factors, those that constitute the actin cytoskeletal system of the cell. Our research has indicated that actin cytoskeletal dynamics is a key feature during early infection events, including reverse transcription and nuclear migration within the cell. Our goal is to identify cytoskeletal factors that play pivotal roles in HIV-1 replication and determine the functions of these factors. We have previously identified Cofilin, an actin-depolymerization factor, as a critical factor in early HIV-1 infection events. Much of our research is now focusing on the upstream factors of Cofilin, those being LIMK1/2, p21-activated kinases, and certain cellular phosphatases, among others. Emergently, our goal is to create a framework of understanding on which the development of anti-HIV pharmaceuticals can proceed. In this endeavor, we have sought a degree of reproducibility and accuracy in our research constituting a standard of research quality to which all of our findings are subject.
1. Vorster PJ, Guo J, Yoder A, Wang W, Zheng Y, Xu X, Yu D, Spear M, Wu Y 2011. LIM kinase 1 modulates cortical actin and CXCR4 cycling and is activated by HIV-1 to initiate viral infection. J Biol Chem. 286(14):12554-64.
2. Yoder A, Guo J, Yu D, Cui Z, Zhang XE, Wu Y 2011. Effects of microtubule modulators on HIV-1 infection of transformed and resting CD4 T cells. J Virol. 85(6):3020-4.
3. Guo J, Enos C, Wu Y 2010. Specific marking of HIV-1 positive cells using a Rev-dependent lentiviral vector expressing the green fluorescent protein. J Vis Exp. 23;(43). pii: 2198.
4. Wu Y 2010. Chemokine control of HIV-1 infection: beyond a binding competition. Retrovirology. 7:86.
5. Wu Y, Yoder A 2009. Chemokine coreceptor signaling in HIV-1 infection and pathogenesis. PLoS Pathog. 5(12):e1000520.
6. Yu D, Wang W, Yoder A, Spear M, Wu Y 2009. The HIV envelope but not VSV glycoprotein is capable of mediating HIV latent infection of resting CD4 T cells. PLoS Pathog. 5(10):e1000633.
7. Wu Y 2009. Chemokine receptor signaling and HIV infection. Methods Mol Biol. 571:309-19.
8. Iyer SR, Yu D, Biancotto A, Margolis LB, Wu Y 2009. Measurement of human immunodeficiency virus type 1 preintegration transcription by using Rev-dependent Rev-CEM cells reveals a sizable transcribing DNA population comparable to that from proviral templates. J Virol. 83(17):8662-73.
9. Wu Y 2009. The co-receptor signaling model of HIV-1 pathogenesis in peripheral CD4 T cells. Retrovirology. 6:41.
10. Wu Y, Yoder A, Yu D, Wang W, Liu J, Barrett T, Wheeler D, Schlauch K 2008. Cofilin activation in peripheral CD4 T cells of HIV-1 infected patients: a pilot study. Retrovirology. 5:95.
11. Yoder A, Yu D, Dong L, Iyer SR, Xu X, Kelly J, Liu J, Wang W, Vorster PJ, Agulto L, Stephany DA, Cooper JN, Marsh JW, Wu Y 2008. HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells. Cell. 134(5):782-92.
12. Wu Y 2008. The second chance story of HIV-1 DNA: Unintegrated? Not a problem! Retrovirology. 5:61.
13. Young J, Tang Z, Yu Q, Yu D, Wu Y 2008. Selective killing of HIV-1-positive macrophages and T cells by the Rev-dependent lentivirus carrying anthrolysin O from Bacillus anthracis. Retrovirology. 5:36.
14. Kelly J, Beddall MH, Yu D, Iyer SR, Marsh JW, Wu Y 2008. Human macrophages support persistent transcription from unintegrated HIV-1 DNA. Virology. 372(2):300-12.
15. Wu Y, Beddall MH, Marsh JW 2007. Rev-dependent indicator T cell line. Curr HIV Res. 5(4):394-402.
16. Wu Y, Beddall MH, Marsh JW 2007. Rev-dependent lentiviral expression vector. Retrovirology. 4:12.