AEGiS-PRn: An Important Determinant of HIV-1 Virulence Identified: Role of HIV-1 Nef in Virulence

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

An Important Determinant of HIV-1 Virulence Identified: Role of HIV-1 Nef in Virulence

PRNewswire - Thursday October 15, 1998

MONTREAL, Oct. 15 /CNW-PRN/ - The role of the HIV-1 Nef gene as a major determinant of pathogenicity, independent of its role in virus replication, has been unraveled in an animal model by a Montreal research team lead by Dr. Paul Jolicoeur at the Clinical Research Institute of Montreal. The investigators have found that expression in transgenic mice of only one of the known genes of HIV-1 (Nef) was sufficient to elicit a severe disease, very similar to human AIDS, especially pediatric AIDS. These findings, which provide a novel biological assay for the virulence of different strains of HIV-1, are reported in the October 16, 1998 edition of the journal CELL, one of the most prestigious biomedical journals.

This research was funded by the Medical Research Council of Canada.

FAST OR SLOW PROGRESSION IN MICE DEPENDS ON THE LEVEL OF INTRACELLULAR NEF PROTEIN

"We were quite intrigued and excited by our results", said Dr. Jolicoeur. "When we realized that disease progression was very strongly correlated with the amount of the Nef protein in target cells. This also suggested that some particular Nef protein produced by some strains of HIV-1 may promote a more aggressive course of the disease. If this is what happens in humans, we now have a reliable biological assay for virulence".

HIV-1 NEF LEADS TO HYPERACTIVATION, NOT HYPOACTIVATION, OF SIGNALING MOLECULES IN THE THYMUS

Lead authors, Drs. Zaher Hanna and Denis Kay also from the same Institute, were quite amazed to find that thymic cells of the transgenic mice were hyperactivated and hyperresponsive to signals, suggesting that Nef was interfering with signaling in these cells.

These findings indicate that Nef is likely to be a very important target for future therapy and provide insight on the mechanisms used by the HIV-1 to destroy the immune system.

SOURCE: Clinical Research Institute of Montreal
981015
PR981009

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