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Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6

Nature Medicine volume 3, pages 287–292 (1997)Cite this article

Abstract

Human herpesvirus-8 (HHV-8) has been detected in Kaposi's sarcoma (KS) lesions of all types (AIDS-related, classical and endemic), in body-cavity-based B-cell lymphomas (BCBLs) and in le-sions of multicentric Castleman's disease (MCD). We have identified a major gamma-herpesvirus-divergent locus (DL-B) in HHV-8 DNA encoding several HHV-8 unique open reading frames (ORFs), including a homologue of interleukin-6 (IL-6) and two homologues of macrophage inflammatory protein MIP-1. We show that the HHV-8-encoded IL-6 homologue (vlL-6) shares functional properties with endogenous IL-6 proteins and that both vlL-6 and vMIP-1 transcripts are present at high levels following butyrate induction of an HHV-8+ BCBL cell line. Low amounts of constitutive vlL-6, but not vMIP-1, mRNA were also detected. The presence of a functional IL-6 homologue encoded by HHV-8 may provide a mechanistic model for the hypothesized role of HHV-8 in KS, MCD and BCBL that involves the mitogenic effects of vlL-6 on surrounding cells. MIP-1 proteins may enhance these effects through the chemotactic recruitment of endogenous cy-tokine-producing cells into affected tissues and could potentially influence HIV disease progression in coinfected individuals through interactions with the HIV co-receptor CCR-5.

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Author notes

  1. Vivian R. Ruvolo

    Present address: Sealy Center for Oncology and Hematology, University of Texas Medical Center, Galveston, Texas, 77555, USA

Authors and Affiliations

  1. Department of Oncology Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA

    John Nicholas, Vivian R. Ruvolo, Xiaoyu Wan, Dolores Ciufo & Gary S. Hayward

  2. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA

    Gary S. Hayward

  3. Institute of Human Virology, University of Maryland, Baltimore, Maryland, 21201, USA

    Hong-Guang Guo & Marvin S. Reixz

  4. Department of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA

    William H. Burns, Gordon Sandford & Sara B. Hendrickson

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Nicholas, J., Ruvolo, V., Burns, W. et al. Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. Nat Med 3, 287–292 (1997). https://doi.org/10.1038/nm0397-287

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