Influence of cytokines on SIV replication in macrophages.

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

Influence of cytokines on SIV replication in macrophages.

Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:27 (abstract no. 11). Unique Identifier : AIDSLINE PRIM8/900011
Horvath CJ; Walsh DG; Daniel MD; Sehgal PK; Desrosiers RC; Ringler DJ; Harvard Medical School, New England Regional Primate Research; Center, 1 Pine Hill Dr., Southborough, Mass., USA

Abstract: We and others have previously shown that tissue macrophages represent important targets for SIV replication in vivo and in vitro. Control of lentiviral replication within macrophages is likely influenced by a variety of viral and cellular factors; of these cellular factors, cytokines have received significant attention. We have studied cytokine influence on SIV replication in vitro utilizing alveolar macrophages and uncloned SIVmacMTV, a macrophage-tropic variant. Our approach allows us to quantify viral replication on a per cell basis. Cytokines were added to macrophage cultures for 3 days prior to infection with SIV (2 x 10(3) TCID50/2 x10(6) cells) and continuously thereafter. As reported for HIV replication in macrophages, GMCSF (20 U/ml) resulted in marked increases in SIV gag protein culture supernatants. However, after correcting for differences in total cell number and number of gag-containing cells in the treated and untreated wells (n=3-8), GMCSF did not upregulate cellular SIV replication. Similarly, IL-6 (6.25-100 ng/ml) did not upregulate SIV replication on a per cell basis compared to untreated wells. However, IL-6-treated cultures had significantly greater cytopathic changes compared to infected, untreated cultures. In contrast, interferon-gamma (300 U/ml) greatly decreased replication. Endogenously-produced tumor necrosis factor-alpha (TNF-alpha) did not appear to affect SIV replication in any of these cultures as neutralizing antibodies to TNF-alpha did not significantly alter any of the replication profiles. In summary, these results are in contrast to previously published reports of cytokine control of HIV growth in macrophages, and they stress the importance of cell number analyses in the study of lentiviral replication kinetics in macrophages.

Keywords: Animal Cells, Cultured Cytokines/*PHYSIOLOGY Gene Products, gag/METABOLISM Granulocyte-Macrophage Colony-Stimulating Factor/PHYSIOLOGY Interleukin-6/PHYSIOLOGY Kinetics Macaca Macrophages/*MICROBIOLOGY SIV/*GROWTH & DEVELOPMENT/METABOLISM Tumor Necrosis Factor/PHYSIOLOGY *Virus Replication ABSTRACT
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