@article{6a9ba241ef9f417d9e2d402bb885cee7,
title = "Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain",
abstract = "Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4+ T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizes with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry.",
keywords = "ADAM10, ADAM15, CD4 T lymphocytes, HIV-1 integrase, HIV-1 pre-integration complex (PIC), HIV-1 replication, Macrophages, γ-Secretase",
author = "Endsley, \{Mark A.\} and Somasunderam, \{Anoma D.\} and Guangyu Li and Numan Oezguen and Varatharasa Thiviyanathan and Murray, \{James L.\} and Rubin, \{Donald H.\} and Hodge, \{Thomas W.\} and O'Brien, \{William A.\} and Briana Lewis and Ferguson, \{Monique R.\}",
note = "Funding Information: This work was partly supported by the Public Health Service Grant HL088999 from the National Heart, Lung, and Blood Institute . MAE was also supported by the Public Health Service-NIAID-NIH T32 Training Grant AI007536 . We would like to thank Merck \& Co., Inc. for generously providing raltegravir, the NIH AIDS Research and Reference Reagent Program for providing U1/HIV-1 and U373-MAGI-CCR5 cell lines, Adriana Paulucci-Holthauzen, Ph.D. (Manager of the Optical Microscopy Core at the University of Texas Medical Branch, Galveston, TX) for assistance with confocal microscopy imaging, and Edward Siwak, Ph.D. (Associate Director of Virology Core Facility, Center for AIDS Research at Baylor College of Medicine, Houston, TX) for providing HIV-1 SF162 and HIV-1 89.6 . This project was also partially supported by the Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX .",
year = "2014",
month = apr,
doi = "10.1016/j.virol.2014.02.006",
language = "English (US)",
volume = "454-455",
pages = "60--66",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",
}