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The role of the alternative coreceptor GPR15 in SIV tropism for human cells |
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| Authors: | Miriam Kiene Andrea Marzi Andreas Urbanczyk Stephanie Bertram Tanja Fisch Inga Nehlmeier Kerstin Gnirß Christina B Karsten David Palesch Jan Münch Francesca Chiodi Stefan Pöhlmann Imke Steffen |
| Affiliation: | a Institute of Virology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany b Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-17177 Stockholm, Sweden c Institute of Clinical and Molecular Virology, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany d Infection Biology Unit, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany e Department of Cellular Chemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany f Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081 Ulm, Germany g Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, CA 94118, USA h Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA |
| Abstract: | Many SIV isolates can employ the orphan receptor GPR15 as coreceptor for efficient entry into transfected cell lines, but the role of endogenously expressed GPR15 in SIV cell tropism is largely unclear. Here, we show that several human B and T cell lines express GPR15 on the cell surface, including the T/B cell hybrid cell line CEMx174, and that GPR15 expression is essential for SIV infection of CEMx174 cells. In addition, GPR15 expression was detected on subsets of primary human CD4+, CD8+ and CD19+ peripheral blood mononuclear cells (PBMCs), respectively. However, GPR15+ PBMCs were not efficiently infected by HIV and SIV, including cells from individuals homozygous for the defective Δ32 ccr5 allele. These results suggest that GPR15 is coexpressed with CD4 on PBMCs but that infection of CD4+, GPR15+ cells is not responsible for the well documented ability of SIV to infect CCR5− blood cells. |
| Keywords: | SIV Entry Coreceptor GPR15 CXCR6 |
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