Importance of fibrocytes and macrophages as HIV-1 reservoirs

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03725
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Kumamoto University
• Principal Investigator: Suzu Shinya 熊本大学, ヒトレトロウイルス学共同研究センター, 教授 (80363513)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 潜伏感染 / HIV-1

Outline of Final Research Achievements

Like CD4+ T cells, monocytes serve as HIV-1 reservoirs. Here we show that a monocyte fraction expressing CD34 (＝fibrocytes）is more susceptible to HIV-1 infection than CD34-negative major subset. In viremic patients, CD34+ fraction harbored more proviruses. When compared to the major subset, CD34+ fraction expressed HIV-1 receptors CD4 and CCR5 at higher levels and HIV-1 restriction factors MX2 and SAMHD1 at lower levels. Proviruses was also detected in CD34+ fraction of virologically-suppressed patients. CD34+ monocytes were present in lymph nodes, and expressed CD4 and CCR5 at higher levels than the major subset, as in peripheral blood. Those CD34+ monocytes highly expressed CCR7 and S1PR1, critical regulators of in vivo cellular trafficking. Our findings suggest that CD34+ monocytes are infected with residual HIV-1 after migrating into tissues including lymph nodes and return to circulation, which explains the detection of proviruses in the cells even after long-term ART.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

HIV-の克服には潜伏感染細胞の排除が重要である。静止期CD4+ T細胞以外にも近年、単球への潜伏感染も分かってきた。本研究では単球中ではfibrocytesに潜伏感染しやすいことを明らかにした。さらに、長期に抗レトロウイルス療法を行い、血中ウイルス量が検出限界以下になった感染者において、なぜ末梢fibrocytesにHIV-1ウイルスゲノムが存在し得るのかは不明であったが、この根源的な疑問にも一定の答えを出せた。並行して進めた組織マクロファージ解析も合わせ、ミエロイド系の細胞に関する一連の発見はHIV-1潜伏感染細胞の完全排除に向けて、有用かつ重要な情報と期待される。