Title
Nuclear Trafficking of the HIV-1 Pre-Integration Complex Depends on the ADAM10 Intracellular Domain
Document Type
Article
Publication Date
4-1-2014
Description
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.
Citation Information
Endsley, Mark A.; Somasunderam, Anoma D.; Li, Guangyu; Oezguen, Numan; Thiviyanathan, Varatharasa; Murray, James L.; Rubin, Donald H.; Hodge, Thomas W.; O'Brien, William A.; Lewis, Briana; and Ferguson, Monique R.. 2014. Nuclear Trafficking of the HIV-1 Pre-Integration Complex Depends on the ADAM10 Intracellular Domain. Virology. Vol.454-455(1). 60-66. https://doi.org/10.1016/j.virol.2014.02.006 PMID: 24725932 ISSN: 0042-6822