アクティブボード・2017年12月
     ・・・・・2017年12月 1日作成・・・・・
研究発表を行った学会;
   第65回日本ウイルス学会学術集会
   2017年10月24日〜26日(大阪)
タイトル;Latent HIV-1 infection in fibrocytes in vivo.
発表者;野依 修 氏
   (熊本大学 エイズ学研究センター 鈴研究室)
要旨;
Background: Continuous ART treatment sufficiently suppresses HIV-1 replication but viral rebound occurs by the interruption of ART treatment. While resting CD4+ T cells are one of the best investigated cells as reservoir, increasing evidences show that latent HIV-1 persists in other cells such as monocytes and macrophages. We reported that fibrocytes with the characteristic of macrophages and fibroblasts are long-lived persistently infected cells causing long-term HIV-1 production at low but steady level. In the present study, we further investigated the contribution of fibrocytes to HIV-1 latency in ART-treated patients. Materials and Methods: PBMCs from chronically HIV-1-infected Japanese patients with the treatment of ART were used for CD3-CD14+CD16-CD34+ fibrocyte-enriched fraction and CD25-CD69-HLA-DR-CD4+ resting T cells sorting and the percentage of CD34+ cells in CD3-CD14+CD16- cells was calculated. HIV-1 provirus was detected by modified Alu-PCR method.
Results and Discussion: Proviral DNA was highly detected in fibrocytes than in monocytes in consistence with the expression level of HIV-1 receptor and coreceptors on these cells. But, HIV-1-exposed fibrocytes produced lower amount of Gag than monocytes. Similarly, when cells were infected with HIV-1 following differentiation in fibrocytes- or macrophages-inducing culture medium, lower amount of Gag was detected in former condition despite proviral DNA was sufficiently integrated. Importantly, higher percentage of virus-infected fibrocytes could survive longer than that of macrophages with long-term HIV-1 production at low but steady level. In vivo, we found that the percentage of fibrocytes in monocytes correlates well with state of disease and that the frequency of proviral DNA in fibrocytes was higher, or at least comparable, compared with that in resting CD4+ T cells. Collectively, fibrocytes exhibited persistently infected cell-like phenotypes and is presumed to be involved in HIV-1 latent infection.