Dr Yasuhiro Takeuchi
Reader in Molecular Virology
Yasuhiro Takeuchi has been based in London, UK for 23 years initially at Institute of Cancer Research and then UCL. He studied Biochemistry at University of Tokyo and obtained MSc on physicochemical study of nucleic acids and then PhD on molecular biology of small nuclear RNA. He started his research on retroviruses upon the appointment as a junior lecturer at Gunma University, Japan in 1986. Since then he has been working on human viruses, HIV and HTLV and mammalian gammaretroviruses including porcine endogenous retroviruses. His research on retrovirus biology has concerned several aspects of infection and evolution with an emphasis on envelope-receptor interaction. The applied side of the research has been focused on the use of retroviruses as vectors for gene therapy and zoonotic infection in xenotransplantation. Since September 2016 Yasu has been 30% seconded to Advanced Therapies, National Institute for Biological Standards and Control (NIBSC).
- Early HIV studies: I contributed to HIV research in late 1980s and 1990s. A biochemical study revealed that HIV reverse transcriptase has low fidelity, potentially contributing to HIV's fast evolution and vast genetic heterogeneity (e). In molecular biology studies, I made a pair of infectious HIV molecular clones with different cell tropism caused by a single point mutation in the env gene (f). This particular mutation can result in both cell tropism change and neutralizing antibody escape (g). This tropism difference was later attributed to difference in co-receptor usage (h).
- Retroviral pseudotypes: I have developed various types of retroviral pseudotypes which encode a marker gene based on murine leukemia virus (MLV) vector but bear various types of envelope proteins, initially related gammaretroviral envelopes (i). Using these pseudotypes I have shown viruses that have certain viral envelopes and/or are produced in certain cell lines are inactivated in fresh human serum with intact complement activity (c above and j). This pseudotyping technology has been expanded to non-retroviral envelopes, e.g. SARS (j) and influenza (l), and applied for serological studies.
- Gene therapy vectorology: In a long standing collaboration with Mary Collins, we have established a series of stable vector packaging cell lines; gammaretroviral (m) and lentiviral (a, b above and n). Our unique system for continuous production of lentiviral vectors can reduce the cost of vector production. We also have a track record of insertional mutagenesis studies in the vector safety area (d above o and p). These studies concern expression/activation of proviruses, interest shared by the HIV cure field.
- Retrovirus receptors: As another area of studies using retroviral pseudotypes, I have contributed to identification and characterization of retroviral receptors, including a lentivirus (FIV, q). The work on porcine endogenous retrovirus receptors (s and t) is in the context of my studies on xenotransplantation, see below.
- Xenotransplantation: With a safety concern of pig-to-human xenotransplantation, we started to study porcine endogenous retroviruses in mid 1990s and reported their ability to infect human cells in vitro (u and v). While our initial studies made the field aware of the importance of safety studies, this series of studies around xenotransplantation have been expanded. I contributed some interpretation of pig whole genome sequence (w) and identification of anti-glycan antibodies that were induced by and are present long after exposure to live pig skin (x). Prevention of immune responses to these antigens is currently a hot topic in the xenotransplantation field.
- Takeuchi Y, Nagumo T, Hoshino H. Low fidelity of cell-free DNA synthesis by reverse transcriptase of human immunodeficiency virus. J Virol. 1988;62:3900-3902
- Takeuchi Y, Akutsu M, Murayama K, et al. Host range mutant of human immunodeficiency virus type 1: modification of cell tropism by a single point mutation at the neutralization epitope in the env gene. J Virol. 1991;65:1710-1718
- McKnight A, Weiss RA, Shotton C, Takeuchi Y, Hoshino H, Clapham PR. Change in tropism upon immune escape by human immunodeficiency virus. J Virol. 1995;69:3167-3170
- Shimizu N, Haraguchi Y, Takeuchi Y, et al. Changes in and discrepancies between cell tropisms and coreceptor uses of human immunodeficiency virus type 1 induced by single point mutations at the V3 tip of the env protein. Virology. 1999;259:324-333
- Takeuchi Y, Simpson G, Vile RG, et al. Retroviral pseudotypes produced by rescue of a Moloney murine leukemia virus vector by C-type, but not D-type, retroviruses. Virology. 1992;186:792-794
- Takeuchi Y, Liong SH, Bieniasz PD, et al. Sensitization of rhabdo-, lenti-, and spumaviruses to human serum by galactosyl(alpha1-3)galactosylation. J Virol. 1997;71:6174-6178
- Temperton NJ, Chan PK, Simmons G, Zambon MC, Tedder RD, Takeuchi Y, Weiss RA. Longitudinally profiling neutralizing antibody response to SARS coronavirus with pseudotypes. Emerg Infect Dis. 2005;11:411-416
- Temperton NJ, Hoschler K, Major D, Nicolson C, Manvell R, Hien VM, Ha do Q, de Jong M, Zambon M, Takeuchi Y, Weiss RA. A sensitive retroviral pseudotype assay for Influenza H5N1 neutralizing antibodies. Influenza Other Respi Viruses. 2007;1:105-112
- Cosset FL, Takeuchi Y, Weiss RA, Collins MK. High-titer packaging cells producing recombinant retroviruses resistant to human serum. J Virol. 1995;69:7430-7436
- Ikeda Y, Takeuchi Y, Martin F, Cosset FL, Mitrophanous K, Collins M. Continuous high-titer HIV-1 vector production. Nat Biotechnol. 2003;21:569-572
- Bokhoven M, Stephen SL, Knight S, Gevers EF, Robinson IC, Takeuchi Y, Collins MK. Insertional gene activation by lentiviral and gammaretroviral vectors. J Virol. 2009;83:283-294
- Knight S, Collins M, Takeuchi Y. Insertional mutagenesis by retroviral vectors: current concepts and methods of analysis. Curr Gene Ther. 2013;13:211-227
- Shimojima M, Miyazawa T, Ikeda Y, McMonagle EL, Haining H, Akashi H, Takeuchi Y, Hosie MJ, Willett BJ. Use of CD134 as a primary receptor by the feline immunodeficiency virus. Science. 2004;303:1192-1195
- Tailor CS, Nouri A, Zhao Y, Takeuchi Y, Kabat D. A sodium-dependent neutral-amino-acid transporter mediates infections of feline and baboon endogenous retroviruses and simian type D retroviruses. J Virol. 1999;73:4470-4474
- Takeuchi Y, Patience C, Magre S, Weiss RA, Banerjee PT, Le Tissier P, Stoye JP. Host range and interference studies of three classes of pig endogenous retrovirus. J Virol. 1998;72:9986-9991
- Ericsson TA, Takeuchi Y, Templin C, et al. Identification of receptors for pig endogenous retrovirus. Proc Natl Acad Sci U S A. 2003;100:6759-6764
- Patience C, Takeuchi Y, Weiss RA. Infection of human cells by an endogenous retrovirus of pigs. Nat Med. 1997;3:282-286
- Le Tissier P, Stoye JP, Takeuchi Y, Patience C, Weiss RA. Two sets of human-tropic pig retrovirus. Nature. 1997;389:681-682
- Groenen MA, Archibald AL, Uenishi H, et al. (YT, Leader on PERV and retroviral insertions). Analyses of pig genomes provide insight into porcine demography and evolution. Nature. 2012;491:393-398
- Scobie L, Padler-Karavani V, Le Bas-Bernardet S, et al. (YT, corresponding author). Long-term IgG response to porcine Neu5Gc antigens without transmission of PERV in burn patients treated with porcine skin xenografts. J Immunol. 2013;191:2907-2915.
A full list of publications can be accessed via UCL IRIS.