Kaposi's Sarcoma-Associated Human herpesvirus-8 Encodes Homologues of Macrophage Inflammatory protein-1 and interleukin-6

Nat Med. 1997 Mar;3(3):287-92. doi: 10.1038/nm0397-287.

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 lesions 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 (vIL-6) shares functional properties with endogenous IL-6 proteins and that both vIL-6 and vMIP-1 transcripts are present at high levels following butyrate induction of an HHV-8' BCBL cell line. Low amounts of constitutive vIL-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 vIL-6 on surrounding cells. MIP-1 proteins may enhance these effects through the chemotactic recruitment of endogenous cytokine-producing cells into affected tissues and could potentially influence HIV disease progression in coinfected individuals through interactions with the HIV co-receptor CCR-5.

MeSH terms

  • Amino Acid Sequence
  • Chemokine CCL4
  • DNA, Viral / genetics*
  • Herpesvirus 8, Human / genetics*
  • Humans
  • Interleukin-6 / genetics*
  • Macrophage Inflammatory Proteins / genetics*
  • Molecular Sequence Data
  • RNA, Messenger / analysis
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid

Substances

  • Chemokine CCL4
  • DNA, Viral
  • Interleukin-6
  • Macrophage Inflammatory Proteins
  • RNA, Messenger

Associated data

  • GENBANK/U67774
  • GENBANK/U67775
  • GENBANK/U74585