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研究発表を行った学会；
・10th DGFI Spring School on Immunology
　２０１４年３月９日〜１４日（エタール、ドイツ）
・第61回日本ウイルス学会
　２０１３年１１月１０日〜１２日（神戸）
タイトル；HIV-1 restriction factor, Murr1 (COMMD1), suppresses Toll-like receptor signaling in HIV-1 latently infected cells.
発表者；工藤　絵里子　氏
　　　（熊本大学　エイズ学研究センター 岡田プロジェクト研究室）
Abstract；
Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities, but cannot eradicate HIV-1 in HIV/AIDS patients. Toll-like receptor (TLR), one of the pattern recognition receptors (PRRs), plays a role of the first line host protection from pathogens such as bacteria and virus by cytokine induction. TLR7 and TLR8 recognize HIV-1 single-stranded RNA (ssRNA) and induce NF-κB and IRF7 transcriptional activation. Despite host cells have these antiviral innate immune system, there is no report revealing that why HIV-1 latently infected cells are established. In this study, we focused on the innate immune system, especially TLRs, and investigated effect for HIV-1 latently infected cells compared with parental cells.
First, we compared all of TLRs ligand responses between HIV-1 latently infected cells, U1, and its parental cells, U937, observing TNF-α and IL-6 mRNA expression by Q-PCR. All of TLRs ligand response was lower in U1 cells than U937 cells, especially TLR7/8. NF-κB-mediated TLR signaling was also suppressed in U1 cells compared with U937 cells. Moreover, we compared the expression level of IκBα protein and the stability of IκBα protein between 4 latently infected cell lines (U1, OM10.1, J1.1 and ACH-2 cells) and each parental cell line (U937, HL60, Jurkat and A3.01 cells) with cycloheximide chase assay which inhibits de novo protein synthesis. The expression and stability of IκBα protein was higher in latently infected myeloid cell lines (U1 and OM10.1 cells), but not in latently infected T cell lines (J1.1 and ACH-2 cells). To clarify the mechanism of IκBα protein stability, we examined some relative factors. As a result, expression of Murr1 (COMMD1) was induced in latently infected myeloid cell lines. This gene was reported as HIV-1 replication inhibitor through suppression of NF-κB activity (Green WC, Nat Immunol, 2004). Moreover, to examine effect of IκBα protein expression by knockdown of Murr1 using siRNA, U1 cells treated siRNA targeting Murr1. As a result, Murr1 knockdown cells induced reduction of IκBα protein.
These data show that suppression of NF-κB signaling is induced by Murr1-mediated stability of IκBα in HIV-1 latently infected cells. Recent study reported that knockdown of IκBα with siRNA induces HIV-1 reactivation in HIV-1 latency. Our data demonstrate that stability of IκBα by Murr1 is important for maintaining HIV-1 latency in myeloid cells.