Important note: Information in this article was accurate in September 2004. The state of the art may have changed since the publication date.
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AIDSWEEKLY Plus; Monday, September 20, 2004
Staff Medical Writers
"Although cells of monocytic lineage are the primary source of human immunodeficiency virus type 1 (HIV-1) in the brain, other cell types in the central nervous system, including astrocytes, can harbor a latent or persistent HIV-1 infection.
"In the present study, we examined whether immature, multipotential human brain-derived progenitor cells (nestin positive) are also permissive for infection," scientists in the United States report.
"When exposed to IIIB and NL4-3 strains of HIV-1, progenitor cells and progenitor-derived astrocytes became infected, with peak p24 levels of 100 to 500 pg/ml at 3 to 6 days postinfection. After 10 days," wrote D.M.P. Lawrence and coworkers, "virus production was undetectable but could be stimulated by the addition of tumor necrosis factor alpha (TNF-alpha)."
"To bypass limitations to receptor entry, we compared the fate of infection in these cell populations by transfection with the infectious HIV-1 clone, pNL4-3. Again, transfected progenitors and astrocytes produced virus for 7 days but diminished to low levels beyond 8 days post-transfection.
"During the nonproductive phase," said investigators, "TNF-alpha stimulated virus production from progenitors as late as 5 weeks posttransfection. Astrocytes produced 5- to 20-fold more infectious virus (27 ng of p24/106 cells) than progenitors at the peak of 3 days posttransfection."
"Differentiation of infected progenitors toward an astrocyte phenotype increased virus production to levels consistent with infected astrocytes," the authors continued, "suggesting a phenotypic difference in viral replication."
"Using this cell culture system of multipotential human brain-derived progenitor cells, we provide evidence that progenitor cells may be a reservoir for HIV-1 in the brains of AIDS patients," Lawrence concluded.
Lawrence and colleagues published their study in Journal of Virology (Human immunodeficiency virus type 1 infection of human brain-derived progenitor cells. J Virol. 2004 Jul;78(14):7319-28.
For more information, contact E.O. Major, NINDS, Laboratory of Molecular Medicine and Neuroscience, NIH, 36 Convent Dr., MSC 4164, Bldg. 36, Rm. 5W21, Bethesda, MD 20892 USA.
Publisher contact information for the Journal of Virology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904 USA.
The information in this article comes under the major subject areas of AIDS/HIV, Immunology, Neuroscience, Stem Cell Research, and Virology.
This article was prepared by AIDS Weekly editors from staff and other reports.
Reference
Lawrence DM, Durham LC, Schwartz L, et al., "Human immunodeficiency virus type 1 infection of human brain-derived progenitor cells", J Virol. 2004 Jul;78(14):7319-28.
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