Stimulation of B lymphocytes by cmvIL-10 but not LAcmvIL-10.
Human cytomegalovirus (HCMV) is a widespread pathogen that establishes lifelong latent infection facilitated by numerous mechanisms for modulating the host immune system. The UL111A region of the HCMV genome encodes a homolog of human cellular IL-10 (hIL-10). The viral cytokine, cmvIL-10, exhibits many of the immunosuppressive properties of hIL-10. However, hIL-10 is also known to have stimulatory effects on B lymphocytes. We found that cmvIL-10 has the ability to enhance B cell proliferation, despite having only 27% sequence identity to hIL-10. Treatment with cmvIL-10 stimulated autocrine production of hIL-10 by B lymphocytes and led to activation of the latent transcription factor Stat3. In contrast, LAcmvIL-10, a truncated protein resulting from an alternatively spliced transcript in latently infected cells, did not stimulate B cell proliferation, Stat3 activation, or hIL-10 production. These results provide insights into the biological activity of the full-length and latency-associated viral cytokines and suggest different roles for each in HCMV infection.
Spencer
Juliet V
JV
Department of Biology, University of San Francisco, 2130 Fulton St., Harney Science Center Room 342, San Francisco, CA 94117, USA. jspencer@usfca.edu
Cadaoas
Jaclyn
J
Castillo
Patricia R
PR
Saini
Vandana
V
Slobedman
Barry
B
D001402:B-Lymphocytes / Q000821:virology*; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014764:Viral Proteins / Q000276:immunology*
C446339:CMV IL-10 protein, Cytomegalovirus; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014764:Viral Proteins; D016753:Interleukin-10