Marc-André Langlois, PhD.
Assistant Professor / Principal Investigator
Emerging Pathogens Research Institute
Department of Pathology and Laboratory Medicine
Faculty of Medicine.
451 Smyth Road, Room 4160
Ottawa, Ontario, K1H 8M5, Canada
Tel: (613) 562 5800 ext. 7110 (Office) Ext. 7111 (Lab)
Fax: (613) 562-5442
LABORATORY OF MOLECULAR VIROLOGY AND INTRINSIC IMMUNITY
Areas of Interest and Expertise:
Intrinsic immunity represents the collection of continuously active mechanisms that protect a host from viral pathogens. This unique feature of intrinsic immunity sets it apart from conventional adaptive and innate immune responses in that it does not require priming by the recognition of viral epitopes or pathogen associated molecular patterns (PAMPS), nor does it require a downstream cascade of signaling events.
Host-encoded intrinsic restriction factors are proteins that constitute the first line of defense against viral pathogens that a host has never encountered before; and the only line of defense against those that can evade conventional immune responses. These intrinsic restriction factors are especially effective against retroviruses which can rapidly infect and replicate and then propagate infection.
APOBEC3 proteins are potent intrinsic restriction factors expressed in T-cells, B-cells and a broad range of other cells and tissues in mammals. They can act during retroviral replication to generate inactivating mutations in the genome of incoming retroviruses. They are believed to play a major role in protecting humans against retroviruses of human or animal origin and against endogenous retroelement transposition in the genome.
The focus of our research is to understand how certain human viral pathogens, such as HIV, overcome restriction by these potent host-encoded antiviral factors. My lab is specifically interested in:
- Determining how APOBEC3 proteins are regulated;
- Identifying cellular factors that interact with both APOBEC3 and viral proteins such as HIV Vif;
- Developing new approaches that will solicit intrinsic and innate immunity to eliminate retroviral pathogens;
- Establishing small animal models to test these new approaches.
Langlois, M.A., Kemmerich, K, Rada,C and Neuberger, M.S. (2009) The AKV murine leukemia virus is restricted and hypermutated by mouse APOBEC3. Journal of Virology, November, 83(22): 430 - 439
Langlois, M.A. and Neuberger, M.S. (2008) Human APOBEC3G can restrict Infection in avian cells and acts independently of both UNG and SMUG1. Journal of Virology. May, 82 (9): 4660-4664.
Takeda, E., Tsuji-Kawahara, S., Sakamoto, Langlois, M.A., Neuberger, M.S., Rada, C. and Miyazawa, M. (2008) Mouse APOBEC3 restricts Friend leukaemia virus infections and pathogenesis in vivo. Journal of Virology. Nov; 82(22):10998-1008.
Conticello, S.G., Langlois, M.A. and Neuberger, M.S. (2007) Insights into DNA deaminases. Nature Structural and Molecular Biology. Jan; 14(1): 7-9.
- Langlois, M.A., Beale, R.C., Conticello, S.G., and Neuberger, M.S. (2005) Mutational comparaison of the single-domained APOBEC3C and double-domained APOBEC3F/3G antiretroviral cytidine deaminases provides insight into their DNA target site specificities. Nucleic Acids Research. April 4, 33 (6): 1913-1923.
- Conticello, S.G., Langlois, M.A., Yang, Z. and Neuberger, M.S. (2007) In Advances in Immunology. Elsevier Inc. DNA Deamination in Immunity: Aid in the Context of Its APOBEC Relatives. 94:37-73. Review.