Our laboratory studies the molecular mechanisms of exosome biogenesis, as well as the role of exosome biogenesis pathways in cell polarity, cell:cell interactions, intercellular signaling, the biology of HIV and other retroviruses, immunology, evolution, and human disease. Exosomes are small, secreted organelles of ~100nm diameter that have the same topology as the cell and similar molecular properties as retroviral particles. Recent studies from our lab have demonstrated that HIV and other retroviruses are, at their most fundamental level, ‘Trojan exosomes’ that use the normal, non-viral exosome biogenesis pathway for the formation of viral particles. Furthermore, the exosomal origin of HIV and other retroviruses loads them with host-encoded proteins, many of which are polymorphic, and this appears to make these pathogens vulnerable to alloimmune responses during transmission. Questions currently under investigation include:

• Why do cells make exosomes?
• What are the mechanisms of exosome biogenesis?
• What are the mechanisms of exosome uptake by neighboring cells?
• How do viruses exploit exosome biogenesis and exosome uptake mechanisms?
• Which host cell proteins make retroviruses sensitive to alloimmunity?
• How effective is alloimmunization at protecting individuals from retrovirus infection?
• Do pathogenic retroviruses exert frequency-dependent selection for histocompatibility systems, loci, and alleles?

Publications:

Fang Y, Wu N, Gan X, Yan W, Morrell JC, and Gould SJ (2007). Higher-order oligomerization targets plasma membrane proteins and HIV Gag to exosomes. PLoS Biol. In press.

Booth AM, Fang Y, Fallon JK, Yang J-M, Hildreth JEK, and Gould SJ (2006). Exosomes and HIV Gag bud from endosome-like domains of the T-cell plasma membrane. J. Cell Biol. 172:923-935.
PubMed Reference

Gould SJ, Hildreth JEK, and Booth A (2004). The evolution of alloimmunity and the genesis of adaptive immunity. Quarterly Rev. Biol. 79:359-382.
PubMed Reference

Nguyen DG, Booth A, Gould SJ, and Hildreth JE (2003). Evidence that HIV budding in primary macrophages occurs through the exosome release pathway. J. Biol. Chem. 278:52347-52354. PubMed Reference

Gould SJ, Booth A, and Hildreth JEK (2003). The Trojan exosome hypothesis. Proc. Natl. Acad. Sci. USA. 100:10592-10597. PubMed Reference