Open AccessC-C chemokines, pivotal in protection against HIV type 1 infection
Author(s) -
Daniel Zagury,
A Lachgar,
Vida Chams,
Lat S. Fall,
Jacky Bernard,
Jean François Zagury,
B Bizzini,
A. Gringeri,
Elena Santagostino,
Jay Rappaport,
Michaël Feldman,
Stephen J. O’Brien,
Arsène Burny,
Robert C. Gallo
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.7.3857
Subject(s) - chemokine , virus , chemokine receptor , virology , biology , chemokine receptor ccr5 , immunology , mutation , titer , human immunodeficiency virus (hiv) , immune system , gene , genetics
Exposure to HIV type 1 (HIV-1) does not usually lead to infection. Although this could be because of insufficient virus titer, there is now abundant evidence that some individuals resist infection even when directly exposed to a high titer of HIV. This protection recently has been correlated with homozygous mutations of an HIV-1 coreceptor, namely CCR5, the receptor for the beta-chemokines. Moreover, earlier results already had shown that the same chemokines markedly suppress the nonsyncitial inducing variants of HIV-1, the chief virus type transmitted from person to person. CCR5 mutation, as a unique mechanism of protection, is, however, suspect because HIV-1 variants can use other chemokine receptors as their coreceptor. Moreover, recent results have established that infection can indeed sometimes occur with such mutations. Here, we report on transient natural resistance over time of most of 128 hemophiliacs who were inoculated repeatedly with HIV-1-contaminated Factor VIII concentrate from plasma during 1980-1985 before the development of the HIV blood test. Furthermore, and remarkably, 14 subjects remain uninfected to this date, and in these subjects we found homozygous CCR5 mutations in none but in most of them overproduction of beta chemokines. In vitro experiments confirmed the potent anti-HIV suppressive effect of these chemokines.