Biology Faculty Articles

Title

C-C Chemokines, Pivotal in Protection Against HIV Type 1 Infection

Document Type

Article

Publication Date

3-31-1998

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

ISSN

1091-6490

Volume

95

Issue/No.

7

First Page

3857

Last Page

3861

Abstract

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 β-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 β chemokines. In vitro experiments confirmed the potent anti-HIV suppressive effect of these chemokines.

Comments

© 1998 by The National Academy of Sciences

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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