β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection

Title:β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection

Volume: 12 Issue: 3

Author(s): Yosra Aljawai, Maureen H. Richards, Melanie S. Seaton, Srinivas D. Narasipura and Lena Al-Harthi

Affiliation:

Keywords: β-catenin signaling, HIV, macrophages, monocytes, neuroAIDS, viral pathogenesis.

Abstract: 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-1infection 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 β-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 β-catenin signaling than MDMs. Inducing β-catenin in MDMs suppressed HIV-1 replication by 5-fold while inhibiting endogenous β-catenin signaling in monocytes by transfecting with a dominant negative mutant for the downstream effector of β- catenin (TCF-4) promoted productive HIV-1 replication by 6-fold. These findings indicate that β-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.

Cite this article as:

Aljawai Yosra, Richards H. Maureen, Seaton S. Melanie, Narasipura D. Srinivas and Al-Harthi Lena, β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection, Current HIV Research 2014; 12 (3) . https://dx.doi.org/10.2174/1570162X12666140526122249