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The Human Immunodificiency Virus (HIV) attacks the cells of the immune system and destroys them or renders them ineffectual. Acquired Immunodeficiency Syndrome (AIDS) is the final stage in HIV infection. It may appear after 10 to 15 years.
The inherent danger in a virus lies very much in its ability to develop multiple strategies to escape detection by the immune system. HIV is no exception to the rule. HIV is known to mutate and adapt in each individual and his/her major histocompatibility complex (MHC).
HIV is a good example of how a pathogenic agent can evolve and mutate by creating what is known as a new variant, in order to circumvent its host’s immune system.
The molecular basis of the process has not been clearly established hitherto, but this is what researchers have now been able to do. Their work makes it easier to under the mutual adaptation mechanism between the immune system and HIV.
In order to better understand how HIV works, Victor Appay, INSERM Research Director, in collaboration with his colleagues at Cardiff University (United Kingdom), Kumamoto University (Japan) and Monash University (Australia), and with the support of the ANRS, studied the cells of patients whose immune response proved effective against the virus and its variants. These patients, all of them from the ANRS Primary Infection cohort, were monitored from the time primary infection with HIV was diagnosed. The detailed study focused on the response caused by the T CD8+ lymphocytes of patients infected by HIV and in whom these cells were particularly well preserved and functional.
This protective immune response is possible due to certain T CD8+ lymphocytes, that are known as “cross reactive”. They have a receptor on the surface whose structure gives then the special ability to recognise not only the non-mutant virus but even its mutant variants. This discovery is the first to really pinpoint how HIV can be controlled by certain T CD8+ lymphocytes.
The study highlights the complexity of the forces and mechanisms that lead to the development of the virus and the way it alters the immune system during the course of HIV infection. A better understanding of immunological determinants as the basis for control of replication of HIV is essential for the development of effective vaccines. In fact, the choice between immunogens and adjuvants in the development of vaccines against HIV needs to be rationalised in order to encourage the production of T CD8+ lymphocytes that are particularly skilled at recognising the wilder and mutant forms of the virus.
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A molecular basis for the control of pre-immune escape variants by HIV-specific CD8+ T-cells Kristin Ladell1*, Masao Hashimoto2*, Maria Candela Iglesias3*, Pascal G. Wilmann4*, James E. McLaren1, Stéphanie Gras4, Takayuki Chikata2, Nozomi Kuse2, Solène Fastenackels3, Emma Gostick1, John S. Bridgeman1, Vanessa Venturi5, Zaïna Aït Arkoub6, Henri Agut6, David J. van Bockel7, Jorge R. Almeida3,8, Daniel C. Douek8, Laurence Meyer9, Alain Venet9, Masafumi Takiguchi2*, Jamie Rossjohn1,4*, David A. Price1,8* and Victor Appay3,10*
1 Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK 2 Center for AIDS Research, Kumamoto University,
2-2-1 Honjo, Kumamoto, 860-0811, Japan
3 INSERM UMR S 945, Infections and Immunity, Université Pierre et Marie Curie-Paris6, Hôpital Pitié-Salpêtrière, 75013 Paris, France
4 Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria 3800, Australia
5 Computational Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia
6 Virology Laboratory, ER1 DETIV UPMC, Université Pierre et Marie Curie-Paris6, Hôpital Pitié-Salpêtrière, 75013 Paris, France
7 St Vincent’s Centre for Applied Medical Research and University of New South Wales, Darlinghurst, Sydney, New South Wales 2010, Australia
8 Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
9 INSERM, Université Paris-Sud, Hôpital du Kremlin-Bicêtre, 94275 Le Kremlin-Bicêtre, France
10 AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire d’Immunologie Cellulaire et Tissulaire, 75013 Paris, France