AIDSWEEKLY Plus; November 25, 2002
Michael Greer, Senior Medical Writer

"S100A8, S100A9, and S100A12, collectively known as myeloid-related proteins (MRPs), are highly expressed by the myeloid cell lineage and are found in the extracellular milieu during infections and inflammatory conditions," according to Carle Ryckman and colleagues at the University Hospital Complex of Quebec and the University of Laval in St. Foy.

These proteins trigger HIV genetic activity necessary for viral replication, Ryckman and coauthors found.

Previous studies had shown that MRP levels were significantly elevated in HIV patients, the researchers said. These studies also revealed that MRP serum concentrations were correlated with the extent of CD4 cell depletion.

Ryckman and coauthors treated latently infected human T cells with MRPs, which augmented viral replication by up to five times, according to the report. Genetic assays showed that these proteins activate the HIV long terminal repeat (LTR) promoter, and that this effect could be prevented by MRP-specific antibodies.

MRP-induced promoter activity required the viral enhancer sequence and the transcription factor nuclear factor-kappaB (HIV-1 transcription and virus production are both accentuated by the proinflammatory myeloid-related proteins in human CD4+ T lymphocytes. J Immunol 2002 Sep 15;169(6):3307-13.

Ryckman and colleagues concluded that "MRPs induce HIV-1 transcriptional activity and viral replication in infected CD4+ T-lymphocytes at concentrations similar to those found in the serum of HIV-1-infected patients."

The corresponding author for this report is Philippe A. Tessier, Centre de Recherche en Infectiologie, Pavillon Centre Hospitalier de l'Universite Laval, Centre Hospitalier Universitaire de Quebec, 2705 Blvd., St Foy, PQ G1V 4G2, Canada. E-mail: Philippe.Tessier@crchul.ulaval.ca.

Key points reported in this study include:

• Myeloid-related proteins (MRPs) play a key role in the process of HIV replication

• They trigger critical viral transcriptional activity

• HIV replication was augmented up to fivefold in infected human T cells incubated with MRPs and high levels of serum

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

Reference

Ryckman C, Robichaud GA, Roy J, et al., "HIV-1 transcription and virus production are both accentuated by the proinflammatory myeloid-related proteins in human CD4+ T lymphocytes", J Immunol 2002 Sep 15;169(6):3307-13.

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