Associate Professor

Tel: +65 6516 3692
Email: mictyj@nus.edu.sg

After infecting their hosts, viruses encounter the formidable task of having to multiply in the face of a vigorous host response. Importantly, the interaction between virus and host will determine the outcome of the viral infection.  The aim of my laboratory is to understand how viruses, with emphasis on RNA viruses that can infect and cause severe diseases in human, make use of the host cell machineries for their own benefit. Currently, we are working on newly emerged viruses like the severe acute respiratory syndrome coronavirus (SARS-CoV) and H5N1 avian influenza A virus, which cause acute infection.  Another target of our research is the hepatitis C virus (HCV) which causes mainly chronic infection and is a major cause of liver disease worldwide.

We have identified several novel viral-host interactions through yeast-two-hybrid, proteomic and computational approaches.  Currently, we are investigating the impact of these interactions on viral replication and/or pathogenesis.  We intend to use the infectious clones of SARS-CoV and HCV, which can be used to produce these two viruses in cell culture, to determine the consequences of altering specific parts of the viral genome or knocking down host proteins that are known to interact with viral proteins.  The infectious clones may also be used in the screening of siRNA libraries to identify other host factors that contribute to viral replication. 

In addition, we are studying the molecular mechanisms for the modulation of apoptosis during SARS-CoV and HCV infections.  Many virus genomes encode gene products that can modulate apoptosis and the regulation of apoptosis in the infected host is an important determinant in the struggle between virus and host for survival.  Induction of apoptosis in infected cells can contribute directly to viral spread and/or pathogenesis, while inhibition of apoptosis can prevent premature death of the infected cells, allowing the virus to replicate to a high titer or allowing the establishment of a persistent infection.  In addition, emerging evidence suggests that non-apoptotic cell-death pathways, like autophagic cell death and necroptosis (also known as regulated necrosis), are also highly regulated cellular suicide processes and contribute to pathological injury.  Hence, we aim to gain an in-depth understanding of the relationship between the different forms of cell-death and viral infection.  These findings will contribute to a better understanding of the intricate interplay between virus and host and may have implications for the development of antiviral therapeutics and vaccine as well as the design of efficient strategies for disease control.  

Aweya JJ and Tan YJ (2011) Modulation of programmed cell death pathways by the hepatitis C virus. Front Biosci 16:608-618

Karlberg H, Tan YJ and Mirazimi A (2011) Induction of caspase activation and cleavage of the viral nucleocapsid protein in different cell types during Crimean-Congo hemorrhagic fever virus infection. J Biol Chem. 286:3227-3234

Keng CT, Akerström S, Leung CS, Poon LL, Peiris JS, Mirazimi A and Tan YJ (2011) SARS coronavirus 8b reduces viral replication by down-regulating E via an ubiquitin-independent proteasome pathway. Microbes Infect. 13:179-188

Oh HL, Akerström S, Shen S, Bereczky S, Karlberg H, Klingström J, Lal SK, Mirazimi A and Tan Y-J (2010) An antibody against a novel and conserved epitope in the hemagglutinin 1 subunit neutralizes numerous H5N1 influenza viruses. J. Virol. 84:8275-8286. 

Tan Z, Akerstrom S, Wee BY, Lal SK, Mirazimi A and Tan Y-J (2010) A new panel of NS1 antibodies for easy detection and titration of influenza A virus. J. Med. Virol. 82:467-475.

Akerström S, Gunalan V, Keng CT, Tan Y-J and Mirazimi A (2009) Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected. Virology 39:1-9.

Mohd-Ismail NK, Deng L, Sukumaran SK, Yu VC, Hotta H and Tan Y-J (2009) The hepatitis C virus core protein contains a BH3 domain that regulates apoptosis through specific interaction with human Mcl-1. J. Virol. 83:9993-10006.

Dutta S and Tan Y-J (2008) Structural and functional characterization of human SGT and its interaction with Vpu of the human immunodeficiency virus type 1. Biochemistry 47:10123-10131.

Shen S, Mahadevappa G, Oh HLJ, Wee BY, Choi YW, Hwang LA, Lim SG, Hong W, Lal SK and Tan Y-J (2008) Comparing the antibody responses against recombinant hemagglutinin proteins of avian influenza A (H5N1) virus expressed in insect cells and bacteria. J. Med. Virol,, 80:1972-1983.

Tan Y-J, Lim SG, and Hong W (2007) Regulation of cell-death during infection by the severe acute respiratory syndrome coronavirus and other coronaviruses. Cell. Microbiol. 9:2552–2561.

Tan YX, Tan TH, Lee MJ, Tham PY, Gunalan V, Druce J, Birch C, Catton M, Fu NY, Yu VC and Tan Y-J (2007) Induction of apoptosis by the severe acute respiratory syndrome coronavirus 7a protein is dependent on its interaction with the Bcl-XL protein. J. Virol. 81:6346-6355.

Åkerström S, Mirazimi A, and Tan Y-J (2007) Inhibition of SARS-CoV replication cycle by small interference RNAs silencing specific SARS proteins, 7a/7b, 3a/3b and S. Antiviral Res. 73:219-227.

Keng CT, Choi Y–W, Welkers MRA, Chan DZL, Shen S, Lim SG, Hong W and Tan Y-J (2006) The human severe acute respiratory syndrome coronavirus (SARS-CoV) 8b protein is distinct from its counterpart in animal SARS-CoV and down-regulates the expression of the envelope protein in infected cells. Virology 354:132–142.

Tan Y-J, Lim SG and Hong W (2006) Understanding the accessory viral proteins unique to the severe acute respiratory syndrome coronavirus. Antiviral Res. 72:78-88.

Lip K-M, Shen S, Yang X, Keng C-T, Zhang A, Oh HLJ, Li Z-H, Hwang LA, Chou C-F, Fielding BC, Tan THP, Mayrhofer J, Falkner FG, Fu J, Lim SG, Hong W and Tan Y-J (2006) Monoclonal antibodies targeting the HR2 domain and the region immediately upstream of the HR2 of the S protein neutralize in vitro infection of severe acute respiratory syndrome coronavirus. J. Virol. 80:941-950.

Tan Y-J, Tham PY, Chan DZL, Chou C-F, Shen S, Fielding BC, Tan THP, Lim SG and Hong W (2005) The severe acute respiratory syndrome coronavirus 3a protein up-regulates the expression of fibrinogen in lung epithelial cells. J. Virol. 79:10083-10087

Keng C-T, Zhang A, Shen S, Lip KM, Fielding BC, Tan THP, Chou C-F, Loh CB, Wang S, Fu J, Yang X, Lim SG, Hong W and Tan Y-J (2005) Amino acids 1055 to 1192 in the S2 region of SARS coronavirus S protein induces neutralizing antibodies: implications for the development of vaccine and anti-viral agent. J. Virol. 79:3289-3296.

Tan Y-J, Fielding BC, Goh PY, Shen S, Tan THP, Lim SG and Hong W (2004) Over-expression of 7a, a protein specifically encoded by the severe acute respiratory syndrome (SARS)-coronavirus, induces apoptosis via a caspase-dependent pathway. J. Virol. 78:14043-14047.

Tan Y-J, Teng E, Shen S, Tan THP, Goh PY, Fielding BC, Ooi EE, Tan HC, Lim SG, and Hong W (2004) A novel SARS coronavirus protein, U274, is transported to the cell surface and undergoes endocytosis. J. Virol. 78:6723-6734.

Tan Y-J, Lim SP, Ting AE, Goh PY, Tan YH, Lim SG and Hong W (2003) An anti-HIV-1 gp120 antibody expressed as an endocytotic transmembrane protein mediates internalization of HIV-1. Virology 315:80-92.

Tan Y-J, Lim S-P, Ng P, Goh P-Y, Lim SG, Tan YH and Hong W (2003) CD81 engineered with endocytotic signals mediates HCV cell entry: implications for receptor usage by HCV in vivo. Virology 308:250-269.

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