Press release

NATURAL PROTECTION AGAINST HIV/AIDS:
"NATURAL KILLERS" INVOLVED

In spite of repeated exposure to HIV-1 over a number of years, some individuals continue to be seronegative. A study carried out by researchers at the Institut Pasteur suggests that certain cells in our immune system, known as the Natural Killers (NK), are involved in this resistance to the transmission of the virus. This is the first time that these cells in our natural defences have been associated with this phenomenon. These results open up new paths for the study of protection against infection and new grounds for thinking about vaccination strategies against HIV/AIDS. This work, which was published in The Journal of Immunology, received finance from the ANRS (French National Aids Research Agency).

Between 5% and 15% of individuals of different populations at risk (regular partners of seropositive subjects, prostitutes, intravenous drug addicts) show no signs of apparent infection by HIV-1 in spite of many years of exposure. These individuals are known as "exposed not infected" (ENI).

The teams of Gianfranco Pancino and Daniel Scott-Algara in the Retrovirus Biology Unit led by Françoise Barré-Sinoussi, are carrying out research into the immunological causes of this resistance to the transmission of HIV-1. The present study was performed among Vietnamese intravenous drug addicts with high-risk behaviour extending over more than 10 years, in co-operation with the Binh Trieu Hospital and the Institut Pasteur in Ho Chi Minh City. The study looked at 37 exposed not infected (ENI) drug addicts, 10 seropositive drug addicts, and 28 blood donors who were not exposed.

The researchers showed that the activity of certain cells in the immune system, known as the Natural Killers (NK), is at higher levels in ENI subjects: they may secrete molecules inhibiting infection by HIV-1, and are capable of destroying infected cells (cytotoxics). These NK cells form a part of our first line of defence against microbes: innate immunity, that is to say, immediate non-specific immunity, in comparison with specific immunity, known as adaptive immunity, which only achieves full effectiveness after several days from the moment of exposure to a pathogenic agent. This is the first time that their involvement has been demonstrated in a phenomenon involving resistance to and protection against HIV-1.

This work opens up various perspectives. The researchers are now studying the NK cell receptors, in order to characterise the resistance mechanisms, and to find new markers for such protection. The identification of molecules directly involved in the innate defences against HIV has the potential to open up in the end new and unexpected therapeutic strategies. In the field of vaccination research, the results obtained suggest that activating certain innate responses could contribute to protection against HIV, and so underline the importance of research (e.g. in the field of adjuvants) into the role of the NK cells in the induction of specific protective responses.

It should be stressed that protection among the ENIs probably has several causes. A number of different immunological factors have already been studied: other immune cells, the T CD8+ lymphocytes, seem, for example, to secrete HIV-1 inhibiting factors in certain ENIs *. Genetic factors may also play a part in resistance to infection: a mutation in a HIV-1 co-receptor (CCR5) has been found, for example, in 2% to 3% of ENIs of Caucasian origin (and this is absent from the populations of Asia and Africa); intrinsic resistance to viral replication in cells targeted by HIV (the CD4+) has, moreover, been found in other studies*.

Resistance to HIV-1 infection among ENIs has probably, therefore, a multifactorial origin, and it is possible that some of these parameters may vary between different populations and different countries.

Every advance in the understanding of the resistance and protection mechanisms among ENIs can bring invaluable information for the development of vaccination or therapeutic strategies.

That is why this new lead involving the NK cells is so important.

Studies are continuing with the Vietnamese cohort, but also among other populations of ENIs in Cambodia and in the Central African Republic, in order to better define the mechanisms for resistance to HIV-1 tied to these cells in our innate defences.

Sources:

- "Increased NK Cell Activity in HIV-1 Exposed But Uninfected Vietnamese Intravascular Drug Users": The Journal of Immunology. 1 December 2003.

Daniel Scott-Algara (1), Lien X. Truong (2), Pierre Versmisse (1), Annie David (1), Tram T. Luong (2), Ngai V. Nguyen (3), Ioannis Theodoru (4), Françoise Barré-Sinoussi (1) and Gianfranco Pancino (1)

(1) Retrovirus Biology Unit, Institut Pasteur, Paris; (2) Institut Pasteur, Ho Chi Minh City, Vietnam; (3) Binh Trieu Hospital, Ho Chi Minh City, Vietnam; (4) Cell and Tissue Immunology Laboratory, INSERM U 543, Pitié-Salpétrière Hospital, Paris

* See, in particular, a recent study of the same group: "CD4+ cell and CD8+ cell-mediated resistance to HIV-1 infection in exposed uninfected intravascular drug users in Vietnam": AIDS. March 2003, vol 17: 1-10.
Lien X. Truong (1), Tram T. Luong (1), Daniel Scott-Algara (2), Pierre Versmisse (3), Annie David (3), Danielle Perez-Bercoff (3), Ngai V. Nguyen (4), Hung K. Tran (1), Cuc T. Cao (1), Arnaud Fontanet (5), Jean-Yves Follézou (6), Ioannis Theodoru (7), Françoise Barré-Sinoussi (3) and Gianfranco Pancino (3)

(1) Institut Pasteur, Ho Chi Minh City, Vietnam; (2) Immuno-haematology and Immunopathology Unit, Institut Pasteur, Paris; (3) Retrovirus Biology Unit, Institut Pasteur, Paris; (4) Binh Trieu Hospital, Ho Chi Minh City, Vietnam; (5) Epidemiology of Emerging Diseases Unit, Institut Pasteur, Paris; (6) Paul Brousse Hospital, Villejuif; (7) Cell and Tissue Immunology Laboratory, INSERM U 543, Pitié-Salpétrière Hospital, Paris

Contacts :

- Gianfranco Pancino, tel: + 33 (0)1 45 68 87 38, email: gpancino@pasteur.fr
- Daniel Scott-Algara, tel: + 33 (0)1 45 68 82 13, email: scott@pasteur.fr
- Press Office, Institut Pasteur, Paris
Tél : 01 45 68 81 46 ; e-mail : presse@pasteur.fr