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Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

HIV-1 Neutralizing Activity is Correlated with Increased Levels of Chemokines in Saliva of HIV-1-Exposed Uninfected Individuals

Author(s): Taha Hirbod, Camilla Reichard, Klara Hasselrot, Johan Soderlund, Joshua Kimani, Job J. Bwayo, Francis Plummer, Rupert Kaul and Kristina Broliden

Volume 6, Issue 1, 2008

Page: [28 - 33] Pages: 6

DOI: 10.2174/157016208783571964

Price: $65

Abstract

Aim: Mucosal HIV-1 exposure stimulates a variety of mucosal immune responses, including IgA1-mediated virus neutralization, even in the absence of an established infection. We hypothesized that other immune molecules might also contribute to the HIV-1 neutralizing activity observed in the mucosal secretions of HIV-1 exposed uninfected individuals. Methods: Saliva samples were collected from HIV-1 seronegative high-risk female sex workers (FSW) from Nairobi. Samples were also collected from HIV-1 IgG positive FSW and HIV-1 IgG negative low-risk women from the same geographical area. In all samples, IgA2, secretory leukocyte protease inhibitor (SLPI), regulated on activation, normal Tcell expressed and secreted (RANTES), macrophage inflammatory protein 1 alpha and beta (MIP-1αand -β) and monocyte chemoattractant protein-1 (MCP-1) were quantified. The IgA1-depleted saliva samples were subsequently tested for neutralizing capacity in a PBMC-based neutralization assay using a primary HIV-1 clade A isolate to determine biological relevance of the measured molecules. Results: HIV-1 specific neutralization was present in the IgA1-depleted fraction from saliva of both HIV-1 seropositive (9 of 10) and high-risk individuals (36 of 45) but not in HIV-1 IgG-negative control subjects (0 of 8). In the high-risk individuals, higher levels of CC-chemokines were seen in those that could neutralize HIV-1 as compared with those that could not (P < 0.05). Conclusion: The HIV-1 neutralizing activity in saliva of HIV-1- exposed high-risk individuals is not only mediated by IgA1, but is also present in IgA1-depleted fractions and is associated with increased levels of CC-chemokines. Such innate immune factors may be important in limiting HIV-1 mucosal transmission.

Keywords: HIV-1, chemokines, IgA2, Neutralization, SLPI


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