Nef Proteins from Simian Immunodeficiency Viruses Are Tetherin Antagonists
CELL HOST & MICROBE
Authors: Zhang, Fengwen; Wilson, Sam J.; Landford, Wilmina C.; Virgen, Beatriz; Gregory, Devon; Johnson, Marc C.; Munch, Jan; Kirchhoff, Frank; Bieniasz, Paul D.; Hatziioannou, Theodora
Abstract
The tetherin/BST2/CD317 protein blocks the release of HIV-1 and other enveloped viruses by inducing tethering of nascent particles to infected cell surfaces. The HIV-1 Vpu protein antagonizes the antiviral activity of human but not monkey tetherins and many simian immunodeficiency viruses (SIVs) do not encode Vpu. Here, we show that the apparently "missing" antitetherin activity in SIVs has been acquired by several SIV Nef proteins. Specifically, SIVMAC/SIVSMM, SIVAGM, and SIVBLU Nef proteins can suppress tetherin activity. Notably, tetherin antagonism by SIV Nef proteins is species specific, is genetically separable from other Nef activities, and is most evident with simian rather than human tetherin proteins. Accordingly, a critical determinant of sensitivity to SIVMAC Nef in the tetherin cytoplasmic tail is variable in nonhuman primate tetherins and deleted in human tetherin, likely due to selective pressures imposed by viral antagonists, perhaps including Nef proteins.
MOLECULAR-CLONING AND CHROMOSOMAL MAPPING OF A BONE-MARROW STROMAL CELL-SURFACE GENE, BST2, THAT MAY BE INVOLVED IN PRE-B-CELL GROWTH
GENOMICS
Authors: ISHIKAWA, J; KAISHO, T; TOMIZAWA, H; LEE, BO; KOBUNE, Y; INAZAWA, J; ORITANI, K; ITOH, M; OCHI, T; ISHIHARA, K; HIRANO, T
Abstract
Bone marrow stromal cells regulate B-cell growth and development through their surface molecules and cytokines. In this study, we generated a mAb, RS38, that recognized a novel human membrane protein, BST-2, expressed on bone marrow stromal cell lines and synovial cell lines. We cloned a cDNA encoding BST-2 from a rheumatoid arthritis-derived synovial cell line. BST-2 is a 30- to 36-kDa type II transmembrane protein, consisting of 180 amino acids. The BST-2 gene (HGMW-approved symbol BST2) is located on chromosome 19p13.2. BST-2 is expressed not only on certain bone marrow stromal cell lines but also on various normal tissues, although its expression pattern is different from that of another bone marrow stromal cell surface molecule, BST-1. BST-2 surface expression on fibroblast cell lines facilitated the stromal cell dependent growth of a murine bone marrow-derived pre-B-cell line, DW34. The results suggest that BST-2 may be involved in pre-B-cell growth. (C) 1995 Academic Press, Inc.