Assistant Professor
Viral and cellular factors
involved in HIV-1 assembly
Accepting graduate students
Lady Davis Institute
Room 326
3755 Côte Ste-Catherine Road
Montreal, QC H3T 1E2
Tel: (514) 340-8260
Fax: (514) 340-7537
chen [dot] liang [at] mcgill [dot] ca (Email)
Research Orientations
Our research is aimed at elucidating the molecular events that take place during the assembly process of human immunodeficiency virus type 1 (HIV-1). The key player in HIV-1 assembly is the Gag protein that is not only able to generate virus-like particles by itself but is also responsible for bringing into the virus particles the other components such us viral Env and Pol proteins, viral genomic RNA, as well as a number of cellular factors.
Our focus at present is to study the multiple activities of Gag involved in producing infectious HIV-1 particles. The ultimate goal is to identify targets that can be exploited for developing inhibitors to block HIV-1 production. The three ongoing projects in this respect are the following:
1. We aim to determine the crucial roles for the capsid-SP1 boundary region in Gag multimerization, Gag-membrane association as well as Gag-RNA interaction. The importance of this 30-amino-acid short junction region in virus production is well reflected by the fact that 10 out of these 30 amino acids are indispensable for generating virus particles. In addition, a potent HIV-1 inhibitor named P-457 is believed to block maturation of virus particles through targeting this capsid-SP1 boundary domain. Our goal is to delineate whether the capsid-SP1 boundary sequence constitutes an independent assembly domain, and how this region functions in the context of the upstream capsid as well as the downstream nucleocapsid domains.
2. We aim to understand the HIV-1 RNA packaging and dimerization processes in terms of the genetic elements regulating the packaging specificity as well as when and where these two events initiate within cells. The mission of HIV-1 particle is to carry and protect its genetic information encoded within its RNA such that new generation of viruses can be produced upon infection of new hosts. Blocking the encapsidation of viral RNA into virus particles represents an ideal strategy to combat HIV-1 infection. The goal of our study is to identify a target suitable for this purpose.
3. We aim to identify cellular factors that associate with HIV-1 Gag protein and to understand the functions of these factors in HIV-1 replication. The approach we employ is a tandem affinity purification (TAP) procedure followed by the mass spectrometry analysis. To date, we have identified a number of such cellular factors. One example is a group of RNA helicases such as ATP-dependent RNA helicase A, RNA helicase Gualpha, and DEAD box protein 18. We speculate that these RNA helicases are involved in the metabolism of HIV-1 RNA such as RNA folding, RNA trafficking, RNA packaging into virus particles as well as reverse transcription following virus entry.
Selected Recent Publications
Roy BB, Hu J, Guo X, Russell RS, Guo F, Kleiman L, Liang C. Association of RNA helicase A with human immunodeficiency virus type 1 particles. J Biol Chem. 2006 Mar 8; [Epub ahead of print]
Roy BB, Russell RS, Turner D, Liang C. The T12I mutation within the SP1 region of Gag restricts packaging of spliced viral RNA into human immunodeficiency virus type 1 with mutated RNA packaging signals and mutated nucleocapsid sequence. Virology. 2006 Jan 20;344(2):304-14.
Guo X, Liang C. Opposing effects of the M368A point mutation and deletion of the SP1 region on membrane binding of human immunodeficiency virus type 1 Gag. Virology. 2005 May 10;335(2):232-41.
Guo X, Roy BB, Hu J, Roldan A, Wainberg MA, Liang C. The R362A mutation at the C-terminus of CA inhibits packaging of human immunodeficiency virus type 1 RNA. Virology. 2005 Dec 20;343(2):190-200.
Guo X, Roldan A, Hu J, Wainberg MA, Liang C. Mutation of the SP1 sequence impairs both multimerization and membrane-binding activities of human immunodeficiency virus type 1 Gag. J Virol. 2005. 79(3):1803-1812.
Ooms M, Huthoff H, Russell R, Liang C, Berkhout B. A riboswitch regulates RNA dimerization and packaging in human immunodeficiency virus type 1 virions. J Virol. 2004. 78(19):10814-10819.
Guo X, Hu J, Whitney JB, Russell RS, Liang C. Important role for the CA-NC spacer region in the assembly of bovine immunodeficiency virus Gag protein. J Virol. 2004. 78(2):551-560.
Russell RS, Roldan A, Detorio M, Hu J, Wainberg MA, Liang C. Effects of a single amino acid substitution within the p2 region of human immunodeficiency virus type 1 on packaging of spliced viral RNA. J Virol. 2003. 77(24):12986-12995.
Russell RS, Hu J, Beriault V, Mouland AJ, Laughrea M, Kleiman L, Wainberg MA, Liang C. Sequences downstream of the 5' splice donor site are required for both packaging and dimerization of human immunodeficiency virus type 1 RNA. J Virol. 2003. 77(1):84-96.