Retroviruses are enveloped RNA viruses, which comprises a large and diverse family including human immunodeficiency virus 1 (HIV-1), the pathogen of AIDS. Retrovirus assembly and budding is a highly concerted process mediated by specific interactions between viral Gag polyproteins and host cofactors that remain largely undefined. An exciting possibility is that these specific virus-host interfaces might represent targets for the development of preventative or therapeutic strategies against infection

This laboratory primarily focuses on the function of the actin cytoskeleton in retroviral Gag transportation and other cellular proteins that participate in retrovirus assembly and budding. Human immunodeficiency virus-1 (HIV-1) and equine infectious anemia virus (EIAV) will be used in parallel or in combination to examine shared and/or distinct cellular mechanisms for the process. A combination of state-of-the-art biological imaging, cellular and molecular virology, and proteomic approaches is used to characterize these specific virus-host cells interactions.

The ongoing projects include:

1) Characterization of cellular factors that regulate the Gag-actin interactions for Gag polyprotein trafficking. The actin cytoskeleton is a highly dynamic network in response to an array of intra- and inter-cellular signals. The goal of this project is to define the actin modulating proteins that are specifically recruited by retroviruses for intracellular transportation of the Gag polyprotein.

2) Characterization of viral determinants for the actin cytoskeleton association. Results of this and other labs demonstrate that Gag association with the actin cytoskeleton follows Gag-Gag multimerization, indicating that the actin interacting interface might be comprised of Gag oligomers. Chimeric HIV/EIAV Gag constructs will be generated to test which level of Gag oligomerization is essential for actin association.

C. Chen and P. Guo. Sequential action of six DNA-packaging pRNAs during phage phi29 genomic DNA translocation. J.Virol. 71:3864, 1997.

P. Guo, C. Zhang, C. Chen, K. Garver and M. Trottier. Inter-RNA interaction of phage phi29 pRNA to form a hexameric complex for viral DNA translocation. Mol. Cell 2:149, 1998.

T. Mohammad, C. Chen, P. Guo and H. Morrison. Photoinduced cross-linking of nucleic acid by cis-Rh(phen)2Cl2+ and cis-Rh(phen)(phi)Cl2+: a new family of light activatable nucleic acid cross-linking agents. Bioorganic & medicinal Chemistry Letters 9:1703, 1999.

C. Chen, C. Zhang and P. Guo. Sequence Requirement for hand-in-hand interaction in formation of RNA dimers and hexamers to gear Phi29 DNA translocation motor. RNA 5:1, 1999.

C. Chen, S. Sheng, Z. Shao and P. Guo. A dimer as a building block in assembling RNA, A hexamer that gears bacterial virus phi29 DNA-translocating machinery. J. Biol. Chem. 275:17510, 2000.

C. Chen, F. Li and R.C. Montelaro. Functional role of equine infectious anemia virus Gag p9 in viral budding and infection. J. Virol. 75:9762, 2001.

F. Li, C. Chen, B. Puffer and R.C. Montelaro. Functional replacement and positional dependence of homologous and heterologous L-domains in equine infectious virus budding and infection. J. Virol. 76:1569, 2002.

C. Chen and R.C. Montelaro. Characterization of RNA elements that regulate Gag-Pol ribosomal frameshifting in equine infectious anemia virus. J. Virol. 77:10280, 2003.

M. Shehu-Xhilaga, S. Ablan, D. Demirov, C. Chen, R.C. Montelaro R. C. and E.O. Freed. Late domain-dependent inhibition of equine infectious anemia virus budding. J. Virol. 78:724, 2004.

C. Chen, O.A. Weisz, D.B. Stolz, S.C. Watkin and R.C. Montelaro. Differential effects of actin cytoskeleton dynamics on equine infectious anemia virus particle production. J. Virol. 78:882, 2004.