This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Transformation of human T lymphocytes by Herpesvirus saimiri (HVS) is dependent on expression of the viral protein Tip and its manipulation of cellular proteins. Here, we report that the conserved glutamic acid-rich domain of Tip interacted with the retromer subunit Vps35. The retromer complex is required for efficient retrograde transport of the cation-independent mannose-6-phosphate receptor (CI-MPR) from the endosome to the trans-Golgi network. Expression of Tip not only caused redistribution of Vps35 from the early endosome to the lysosome and swelling of the lysosomal compartments, but also drastically inhibited retromer activity as measured by decreased CI-MPR levels and lower activities of cellular lysosomal hydrolases. AIDS related.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000168-47
Application #
7715518
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2008-06-05
Project End
2009-04-30
Budget Start
2008-06-05
Budget End
2009-04-30
Support Year
47
Fiscal Year
2008
Total Cost
$32,442
Indirect Cost
Name
Harvard University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
Duke, Angela N; Meng, Zhiqiang; Platt, Donna M et al. (2018) Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. J Pharmacol Exp Ther 366:145-157
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