Albert Einstein College of Medicine has received a USD 3.2 million NIH R01 grant from the National Institute of Allergy and Infectious Diseases to investigate a previously uncharacterized interaction between a host chromatin remodeling protein and HIV-1's TAR RNA — a finding that could open a new avenue for "block and lock" HIV cure strategies.
The award funds a multi-PI team — virologist Ganjam Kalpana, NMR biophysicist Xiao Heng, and computational structural biologist Xiaoqin Zou — to study how INI1 (SMARCB1), a subunit of the SWI/SNF chromatin remodeling complex, interacts directly with TAR RNA to regulate HIV-1 transcriptional elongation. The team reports that INI1's N-terminal winged helix DNA-binding domain binds TAR RNA and that this interaction appears necessary for recruiting the PBAF chromatin remodeling complex to the HIV-1 long terminal repeat, facilitating viral transcription. Disrupting the interaction, the investigators hypothesize, could enforce transcriptional silencing of latent proviruses — supporting deep latency rather than reactivation. The project will combine alanine-scanning mutagenesis, NMR structural determination, and computational modeling to characterize the INI1–TAR complex and test TAR-interaction-defective INI1 mutants in latency models.
The approach is notable because INI1 was previously known primarily for its role in HIV integrase binding and virion morphogenesis, with its function in transcriptional regulation less defined. Identifying the INI1–TAR RNA axis as a potential drug target adds a structurally tractable protein–RNA interaction to the HIV cure toolkit, complementing existing latency-reversing agent strategies. The four-year award runs through May 2030.
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