Abstract
Human herpesvirus-8 (HHV-8/KSHV) is etiologically associated with Kaposi's sarcoma (KS) and other tumors. Constitutive activation of the mitogen-activated protein kinase (MAPK) signaling pathway has been associated with a variety of tumors, including AIDS-related KS. The oncoprotein Raf is situated at a pivotal position in regulating the MAPK pathway. Hence, we analysed the effect of oncoprotein Raf on HHV-8 infectious entry into target cells. Here we report Raf expression to significantly enhance HHV-8 infection of target cells. These findings implicate a role for Raf not only in the infectious entry of HHV-8 but also in modulating KS pathogenesis.
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Acknowledgements
SMA is the recipient of an institutional research grant from American Cancer Society (IRG-97-149). JAM is supported in part by NIH RO1CA098195. We thank Dr Jeffrey Vieira (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) for GFP-HHV-8 (rKSHV.152) harboring BCBL-1 cells; Dr Martin McMahon (UCSF Comprehensive Cancer Center, San Francisco, CA, USA) for the various retrovirus constructs expressing Raf; Dr Phillip H Pekala, (Brody School of Medicine, Greenville, NC, USA) for the use of OLYMPUS IX50 inverted fluorescent microscope; Dr Vishnu Chintalgattu (Brody School of Medicine) for critically reading this manuscript; and Dr Adrian J Reber (University of Georgia, Athens) for his help with statistics.
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Akula, S., Ford, P., Whitman, A. et al. Raf promotes human herpesvirus-8 (HHV-8/KSHV) infection. Oncogene 23, 5227–5241 (2004). https://doi.org/10.1038/sj.onc.1207643
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DOI: https://doi.org/10.1038/sj.onc.1207643
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