期刊
CURRENT HIV RESEARCH
卷 12, 期 3, 页码 164-173出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1570162X12666140526122249
关键词
beta-catenin signaling; HIV; macrophages; monocytes; neuroAIDS; viral pathogenesis
资金
- NIH [R01 NS060632, R01 NIMH100628, PO1AI082971, F32F32NS080657]
- Chicago Developmental Center for AIDS Research (D-CFAR) [P30 AI 082151]
- NIAID
- NCI
- NIMH
- NIDA
- NICHD
- NHLBI
- NCCAM
Cells of the monocyte/macrophage lineage are an important target for HIV-1 infection. They are often at anatomical sites linked to HIV-1 transmission and are an important vehicle for disseminating HIV-1 throughout the body, including the central nervous system. Monocytes do not support extensive productive HIV-1 replication, but they become more susceptible to HIV-1 infection as they differentiate into macrophages. The mechanisms guiding susceptibility of HIV-1 replication in monocytes versus macrophages are not entirely clear. We determined whether endogenous activity of beta-catenin signaling impacts differential susceptibility of monocytes and monocyte-derived macrophages (MDMs) to productive HIV-1 replication. We show that monocytes have an approximately 4-fold higher activity of beta-catenin signaling than MDMs. Inducing beta-catenin in MDMs suppressed HIV-1 replication by 5-fold while inhibiting endogenous beta-catenin signaling in monocytes by transfecting with a dominant negative mutant for the downstream effector of beta-catenin (TCF-4) promoted productive HIV-1 replication by 6-fold. These findings indicate that beta-catenin/TCF-4 is an important pathway for restricted HIV-1 replication in monocytes and plays a significant role in potentiating HIV-1 replication as monocytes differentiate into macrophages. Targeting this pathway may provide a novel strategy to purge the latent reservoir from monocytes/macrophages, especially in sanctuary sites for HIV-1 such as the central nervous system.
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