Screening of epigenetic modifiers identifies novel host-directed agents that suppress HIV-1 replication in primary human macrophages

Epigenetic modifiers were screened to uncover novel agents capable of suppressing HIV-1 replication within primary human macrophages. Epigenetic modifications have a significant impact on various biological processes, including the establishment and maintenance of HIV-1 latency in lymphoid and myeloid cells. Therefore, epigenetic targets hold promise as potential candidates for host-directed therapy.

To investigate this, researchers established an in vitro screening platform utilizing human primary macrophages, encompassing both monocyte-derived and alveolar macrophages, which were infected with a replication-competent luminescent virus. Unlike previous screening methods, this platform enables the identification of compounds and epigenetic targets that modulate viral replication throughout the course of an ongoing infection, encompassing not only transcriptional regulation but also other vulnerabilities across the entire HIV-1 life cycle.

The findings indicate the presence of multiple novel compounds that target unique epigenetic regulators, effectively inhibiting viral replication at various stages within primary macrophages. These promising compounds may emerge as viable candidates or targets for host-directed therapy aimed at combating HIV-1 infection.