Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6.
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.
Nicholas
J
J
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Ruvolo
V R
VR
Burns
W H
WH
Sandford
G
G
Wan
X
X
Ciufo
D
D
Hendrickson
S B
SB
Guo
H G
HG
Hayward
G S
GS
Reitz
M S
MS
D000595:Amino Acid Sequence; D054407:Chemokine CCL4; D004279:DNA, Viral / Q000235:genetics*; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D054407:Chemokine CCL4; D004279:DNA, Viral; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger