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Genetic cause of innate resistance to HIV/AIDS

16.07.2008
MUHC and CHUM researchers demonstrate how two specific genes are involved in an innate resistance to HIV infection.

Some people may be naturally resistant to infection with HIV, the virus that causes AIDS. The results of a study conducted by Dr. Nicole Bernard of the Research Institute of the McGill University Health Centre (MUHC) bring us closer to a genetic explanation. Her study findings were published on July 16 in the journal AIDS.

The simultaneous expression of certain versions of two specific genes called KIR3DL1 and HLA-B*57 is thought to be at the root of some cases of this innate resistance to HIV infection. Depending on which versions of these two genes the patient has, he or she will resist HIV infection or develop AIDS at a slower rate.

These results were obtained by comparing the genetic profiles of people undergoing primary HIV infection ( in their first year of infection) to those repeatedly exposed to HIV but non-infected. The group of exposed but non-infected patients came from a cohort studied by Dr. Julie Bruneau of the Centre hospitalier de l'Université de Montréal. The cohort of primary HIV infected patients is studied by Dr. Jean-Pierre Routy, from the MUHC. Analyses show that the "good" versions of both genes were present in 12.2% of exposed but non-infected subjects versus only 2.7% in patients in primary HIV infection.

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As of yet, no study has clearly described the mechanism of this protection. The KIR3DL1 gene codes for a receptor on the surface of the immune system's natural killer (NK) cells, which when activated destroy infected cells in the body. The HLA-B*57 gene codes for a protein normally found on the surface of all body cells that binds the KIR3DL1 and dampens NK cell activity. The most likely hypothesis is that HIV prevents the HLA-B*57-encoded protein from being expressed on the surface of the infected cells, making it unavailable to bind KIR3DL1. As a consequence, the NK cells retain their activity and destroy the virus-infected cells.

As this mechanism can occur very soon after the virus has started to infect the body cells, people carrying those versions of the 2 genes may be able to destroy more efficiently the infected cells following exposure to HIV, thus lowering their chances of developing AIDS. "More research is needed to determine the exact mechanism behind the protection we have observed, but these findings have revealed a promising avenue," according to Dr. Bernard.

This study opens the way for new ideas in the fight against HIV infection. "In the future, our findings could be used to somehow 'boost' the innate immune system and thus fight the virus as soon as it enters the body," said Dr. Bernard.

Dr. Nicole Bernard is a researcher in the Infection and Immunity Axis of the Research Institute of the McGill University Health Centre (RI MUHC) and a member of the McGill AIDS Centre. She is also an Associate Professor of Medicine at the Faculty of Medicine of McGill University.

Dr. Julie Bruneau is a practitioner at the Service de médecine des toxicomanies of the Centre hospitalier de l'Université de Montréal (CHUM) and Assistant Scientific Director of Clinical Research of the Centre de recherche du CHUM. She is also Associate professor at the department of family medicine, Université de Montréal

Dr Jean-Pierre Routy is an investigator in the Infection and Immunity Axis of the RI MUHC, and an Associate Professor of haematology at the Faculty of Medicine of McGill University.

This study was funded by the Canadian Institutes for Health Research (CIHR) and the Fonds de la recherche en santé du Québec (FRSQ).

The McGill University Health Centre
The McGill University Health Centre (MUHC) is a comprehensive academic health institution with an international reputation for excellence in clinical programs, research and teaching. Its partner hospitals are the Montreal Children's Hospital, the Montreal General Hospital, the Royal Victoria Hospital, the Montreal Neurological Hospital, the Montreal Chest Institute and the Lachine Hospital. The goal of the MUHC is to provide patient care based on the most advanced knowledge in the health care field and to contribute to the development of new knowledge. www.muhc.ca

The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, the university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 600 researchers, nearly 1200 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge. The Research Institute of the MUHC is supported in part by the Fonds de la recherche en santé du Québec.

About CHUM
The Centre hospitalier de l'Université de Montréal (CHUM) provides specialized and ultra-specialized services to a regional and supra-regional clientele. Within its more immediate coverage area, the CHUM also provides general and specialized hospital care and services. The CHUM uses an integrated network model to carry out its five-part mandate of care, teaching, research, the assessment of technologies and health care methodologies, and the promotion of health care. Through its determined efforts to continuously improve quality of care and patient safety, the CHUM has again received accreditation from the Canadian Council on Health Services Accreditation, for the 2007-2010 period. Hôtel-Dieu, Hôpital Notre-Dame, and Hôpital Saint-Luc make up the CHUM, with approximately 10,000 employees, 900 physicians, 270 researchers, 6,000 students and trainees and 700 volunteers providing services to over a million patients each year.

For more information please contact:

Isabelle Kling
Communications Coordinator (research)
MUHC Public Relations and Communications
(514) 843 1560
isabelle.kling@muhc.mcgill.ca
Nathalie Forgue
Communications Advisor
CHUM
514 890-8000, ext. 14342
Pager : 514 801-5762

Isabelle Kling | MUHC
Further information:
http://www.muhc.ca/research
http://www.chumontreal.qc.ca
http://www.muhc.mcgill.ca

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