AIDSWEEKLY Plus; Monday, August 30, 2004
Staff Medical Writers

"Evidence that human progenitor mast cells are susceptible to infection with CCR5-tropic strains of HIV-1 and that circulating HIV-1-infected FcERIalpha+ cells with a similar progenitor phenotype have been isolated from AIDS patients has led to speculation that mast cells may serve as a potential reservoir for infectious HIV-1, wrote scientists in the United States.

"In this study," said J.B. Sundstrom and colleagues, "progenitor mast cells, developed in vitro from CD34+ cord blood stem cells, were experimentally infected with the CCR5-tropic strain HIV-1Bal after 28 days in culture as they reached their HIV-1-susceptible progenitor stage."

"HIV-1 p24 Ag levels were readily detectable by day 7 postinfection (PI), peaked at 2-3 wk PI as mature (tryptase/chymase-positive) HIV-1 infection-resistant mast cells emerged, and then steadily declined to below detectable limits by 10 weeks PI, at which point integrated HIV-1 proviral DNA was confirmed by PCR quantitation in (approximately 34% of) latently infected mast cells," investigators reported.

The authors continued, "Stimulation by ligands for Toll-like receptor (TLR) 2, TLR4, or TLR9 significantly enhanced viral replication in a dose- and time-dependent manner in both HIV-1-infected progenitor and latently infected mature mast cells, without promoting degranulation, apoptosis, cellular proliferation, or dysregulation of TLR agonist-induced cytokine production in infected mast cells.

"Limiting dilution analysis of TLR activated, latently infected mature mast cells indicated that one in four was capable of establishing productive infections in A301 sentinel cells."

"Taken together," Sundstrom concluded, "these results indicate that mast cells may serve both as a viral reservoir and as a model for studying mechanisms of postintegration latency in HIV infection."

Sundstrom and colleagues published their study in Journal of Immunology (Signaling through toll-like receptors triggers HIV-1 replication in latently infected mast cells. J Immunol. 2004 Apr 1;172(7):4391-401.

For more information, contact J.B. Sundstrom, Emory University, School of Medicine, Department of Pathology and Laboratory Medicine, WMB Rm. 2335, 1639 Pierce Dr., Atlanta, GA 30322 USA.

Publisher contact information for the Journal of Immunology is: American Association Immunologists, 9650 Rockville Pike, Bethesda, MD 20814 USA.

The information in this article comes under the major subject areas of Hematology, Immunology, Stem Cell Research, AIDS/HIV, and Virology.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Sundstrom JB, Little DM, Villinger F, "Signaling through Toll-like receptors triggers HIV-1 replication in latently infected mast cells", J Immunol. 2004 Apr 1;172(7):4391-401.

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