Associate ProfessorOffice: MRB 233Phone: 970-491-0726Education: Ph.D., Purdue UniversityEmail: firstname.lastname@example.orgResearch Title: Molecular and Cell Biology of Retrovirus Assembly and Budding
Retroviruses are enveloped RNA viruses, which comprise a large and diverse family including human immunodeficiency virus 1 (HIV-1), the pathogen that leads to AIDS. During the late stage of virus replication, specific and highly concerted interactions among viral components and host cofactors are required for progeny virion assembly and release. An exciting possibility is that these specific virus-host interfaces might represent novel targets for the development of preventative or therapeutic strategies against HIV-1 infection. This laboratory focuses on characterization of the molecular and cellular mechanisms underlying this late stage of HIV-1 replication using a combination of biological imaging, cellular and molecular virology approaches
The ongoing projects include:
1) Mechanistic examination of HIV-1 protease autoprocessing, a viral specific reaction responsible for production of the mature protease. We demonstrated that some residues outside the catalytic site modulate autoprocessing activity. Further illustration of the function of these residues will provide an alternative strategy for anti-HIV development.
2) Identification and characterization of molecules interfering with protease autoprocessing. We have established a functional assay that allows direct quantification of protease autoprocessing in cells. This assay will enable an unprecedented screen for small molecule inhibitors that suppress autoprocessing via a novel interference mechanism. In parallel, we are also in the process of isolating RNA aptamers that would suppress protease autoprocessing.
3) Cytoplasmic expression of RNA aptamers. Different approaches are under investigation for effective delivery of RNA aptamers into the cytoplasm of cell.
Huang LQ, Hall Al, Chen C. Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing. Retrovirology 7:24, 2010.
Chen C, Jin J, Rubin M, Huang L, Sturgeon T, Weixel KM, Stolz DB, Watkins SC, Bamburg JR, Weisz OA, Montelaro RC. Association of Gag multimers with Filamentous Actin during Equine Infectious Anemia Virus Assembly. Curr HIV Res. 5:315-23, 2007 (cover of the issue).
Chen C, Vincent O, Jin J, Weisz OA, Montelaro RC. Functions of early (AP-2) and late (AIP1/ALIX) endocytic proteins in equine infectious anemia virus budding. J Biol Chem 280:40474, 2005.
Chen C, Weisz OA, Stolz DB, Watkin SC, Montelaro RC. Differential effects of actin cytoskeleton dynamics on equine infectious anemia virus particle production. J Virol 78:882, 2004.
Chen C and Montelaro RC. Characterization of RNA elements that regulate Gag-Pol ribosomal frameshifting in equine infectious anemia virus. J Virol 77:10280, 2003.
Li F, Chen C, Puffer BA, Montelaro RC. Functional replacement and positional dependence of homologous and heterologous L-domains in equine infectious virus budding and infection. J Virol 76:1569, 2002.
Chen C, Li F, Montelaro RC. Functional role of equine infectious anemia virus Gag p9 in viral budding and infection. J Virol 75:9762, 2001.
Chen C, Sheng S, Shao Z, Guo P. 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.
Chen C, Zhang C, Guo P. Sequence Requirement for hand-in-hand interaction in formation of RNA dimers and hexamers to gear Phi29 DNA translocation motor. RNA 5:1, 1999.
Guo P, Zhang C, Chen C, Garver K, Trottier M. Inter-RNA interaction of phage phi29 pRNA to form a hexameric complex for viral DNA translocation. Mol Cell 2:149, 1998.
Chen C and Guo P. Sequential action of six DNA-packaging pRNAs during phage phi29 genomic DNA translocation. J Virol 71:3864, 1997.