Human astrocytes inhibit HIV-1 expression in monocyte-derived macrophages by secreted factors.
OBJECTIVE
To determine the effects of primary human fetal and adult astrocytes on HIV-1 replication in monocyte-derived macrophages (MDM).


METHODS
HIV-1 can infect the brain in the early stage of systemic infection. The HIV-1-associated cognitive/motor complex develops later in the course of the disease, suggesting that brain cells may inhibit the early productive infection and the development of neurological disease. In this study, we established an in-vitro coculture system to determine whether astrocytes can modulate HIV-1 replication in MDM.


METHODS
Elutriated human monocytes were differentiated in culture, then infected with monocyte tropic HIV-1. One day after infection, MDM were co-cultured with primary astrocytes. Reverse transcriptase (RT) activity was used to monitor virus replication. RT-polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and bioassay were used to assess cytokine production.


RESULTS
Primary human astrocytes suppressed HIV-1 replication in MDM via the production of soluble factors. Cytokine inhibitors of HIV-1, such as IFN-gamma, IL-4, IL-10 and IL-13, were not detectable, whereas transforming growth factor beta (TGF-beta) was constitutively produced only in its latent form. Paraformaldehyde-fixed astrocytes, unable to secrete cytokines, failed to inhibit HIV-1. These cells caused enhanced virus replication, however, which correlated with an increase in macrophage colony stimulating factor (M-CSF) production.


CONCLUSIONS
Human astrocytes can increase and decrease HIV-1 expression in MDM. An imbalance between the positive and negative effects of astrocytes may contribute to the expression of virus in the brain, and the development of HIV-1-associated cognitive/motor complex.
Hori
K
K
Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA.
Burd
P R
PR
Kutza
J
J
Weih
K A
KA
Clouse
K A
KA
D000328:Adult; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000502:physiology* / Q000821:virology*; D009000:Monocytes / Q000502:physiology*; D014779:Virus Replication
D017077:Culture Media, Conditioned; D016207:Cytokines