A rhesus macaque rhadinovirus related to Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 encodes a functional homologue of interleukin-6.
The rhesus rhadinovirus strain 17577 (RRV strain 17577) genome is essentially colinear with human herpesvirus 8 (HHV8)/Kaposi's sarcoma-associated herpesvirus (KSHV) and encodes several analogous open reading frames (ORFs), including the homologue of cellular interleukin-6 (IL-6). To determine if the RRV IL-6-like ORF (RvIL-6) is biologically functional, it was expressed either transiently in COS-1 cells or purified from bacteria as a glutathione S-transferase (GST)-RvIL-6 fusion and analyzed by IL-6 bioassays. Utilizing the IL-6-dependent B9 cell line, we found that both forms of RvIL-6 supported cell proliferation in a dose-dependent manner. Moreover, antibodies specific to the IL-6 receptor (IL-6R) or the gp130 subunit were capable of blocking the stimulatory effects of RvIL-6. Reciprocal titrations of GST-RvIL-6 against human recombinant IL-6 produced a more-than-additive stimulatory effect, suggesting that RvIL-6 does not inhibit but may instead potentiate normal cellular IL-6 signaling to B cells. These results demonstrate that RRV encodes an accessory protein with IL-6-like activity.
Kaleeba
J A
JA
Division of Pathobiology and Immunology, Oregon Regional Primate Research Center, Beaverton, Oregon 97006, USA.
Bergquam
E P
EP
Wong
S W
SW
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D050822:Cytokine Receptor gp130; D019288:Herpesvirus 8, Human / Q000145:classification; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry* / Q000235:genetics*; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D011995:Recombination, Genetic; D018144:Rhadinovirus / Q000145:classification / Q000235:genetics*; D012514:Sarcoma, Kaposi / Q000821:virology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D014764:Viral Proteins; C120140:interleukin-6, RRV-HHV-8; D050822:Cytokine Receptor gp130