Hypoxia induces lytic replication of Kaposi sarcoma–associated herpesvirus

There is substantial evidence that Kaposi sarcoma–associated herpesvirus (KSHV) plays an important role in the pathogenesis of all forms of Kaposi sarcoma (KS). It has been noted that KS commonly occurs in locations, such as the feet, where tissue may be poorly oxygenated. On the basis of this obser...

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Bibliographic Details
Published in:Blood 2001-05, Vol.97 (10), p.3244-3250
Main Authors: Davis, David A., Rinderknecht, Andrea S., Zoeteweij, J. Paul, Aoki, Yoshiyasu, Read-Connole, Elizabeth L., Tosato, Giovanna, Blauvelt, Andrew, Yarchoan, Robert
Format: Article
Language:English
Subjects:
B-Lymphocytes - virology
Biological and medical sciences
Blotting, Western
Capsid - analysis
Cell Hypoxia
Cell Line
Cobalt - pharmacology
Deferoxamine - pharmacology
Glycoproteins - analysis
Hematologic and hematopoietic diseases
Herpesvirus 8, Human - isolation & purification
Herpesvirus 8, Human - physiology
Humans
Interleukin-6 - metabolism
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Tetradecanoylphorbol Acetate - pharmacology
Tumor Cells, Cultured
Viral Proteins - analysis
Virus Replication - drug effects
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Summary:There is substantial evidence that Kaposi sarcoma–associated herpesvirus (KSHV) plays an important role in the pathogenesis of all forms of Kaposi sarcoma (KS). It has been noted that KS commonly occurs in locations, such as the feet, where tissue may be poorly oxygenated. On the basis of this observation, the potential role of hypoxia in the reactivation of KSHV replication was explored by studying 2 KSHV-infected primary effusion lymphoma B-cell lines (BC-3 and BCBL-1) latently infected with KSHV. Acute and chronic exposure of these cells to hypoxia (1% O2) induced KSHV lytic replication, as indicated by an increase in intracellular lytic protein expression and detection of virus in cell supernatants by Western immunoblotting. In addition, hypoxia increased the levels of secreted viral interleukin-6. Moreover, hypoxia enhanced the lytic replication initiated by the viral inducer 12-O-tetradecanoylphorbol-13-acetate. Desferoxamine and cobalt chloride, 2 compounds that increase the intracellular levels of hypoxia-inducible factor 1, were also able to induce KSHV lytic replication. These studies suggest that hypoxia is an inducer of KSHV replication. This process may play an important role in the pathogenesis of KS.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V97.10.3244