Cytokine influence on simian immunodeficiency virus replication within primary macrophages. TNF-alpha, but not GMCSF, enhances viral replication on a per-cell basis.
The control of HIV-1 or SIV replication within macrophages is probably influenced by a variety of viral and cellular factors. Of the cellular factors, the authors have studied cytokine influence on SIV replication in vitro utilizing simian alveolar macrophages and uncloned SIVmacMTV, a macrophage-tropic variant. The approach allowed quantification of viral replication on a per-cell basis. As reported for HIV-1 replication in macrophages, TNF-alpha significantly increased SIV production in these macrophage cultures. GMCSF also resulted in marked increases in SIV gag protein in culture supernatants. However, after correcting for differences in total cell numbers and numbers of gag-containing cells in the treated and untreated cultures, GMCSF did not upregulate SIV production on a per-cell basis. IL-6 increased SIV replication little if at all but induced significantly greater cytopathic changes in the treated cultures compared with infected, untreated cultures. In contrast, IFN-gamma greatly decreased replication. Our results for GMCSF, IFN-gamma, and IL-6 are in contrast to previously published reports of cytokine control of HIV-1 growth in target cells, and they stress the importance of cell number analyses and the use of primary cultures in the study of lentiviral replication kinetics in macrophages.
Harvard Medical School, Department of Pathology, New England Regional Primate Research Center, Southborough, Massachusetts 01772-9102.
D G
DG
Walsh
C J
CJ
Horvath
A
A
Hansen-Moosa
J J
JJ
MacKey
P K
PK
Sehgal
M D
MD
Daniel
R C
RC
Desrosiers
D J
DJ
Ringler
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects / Q000382:microbiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008253:Macaca mulatta; D008264:Macrophages / Q000382:microbiology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor