HSF1 Activation Can Restrict HIV Replication

Host protein folding stress responses can play important roles in RNA virus replication and evolution. Intriguingly, prior work revealed a complicated interplay between the cytosolic proteostasis stress response, controlled by its master regulator heat shock factor 1 (HSF1) and human immunodeficiency virus-1 (HIV-1). We sought to isolate HSF1 transcription factor activity from proteostasis stress and elucidate the function of HSF1 in HIV-1 lifecycle in absence of cellular stress. We used chemical genetic, stress-independent control of HSF1 activity to establish whether and how HSF1 influences HIV-1 replication. Stress-independent HSF1 induction decreased both the total quantity and infectivity of HIV-1 virions. Moreover, HIV-1 was unable to escape HSF1-mediated restriction over the course of several serial passages. These results promote continued consideration of the heat shock response as a potential target for antiviral drugs. Overall design: RNA-seq characterizing a clonal human T cell line stably expressing doxycycline (dox)-inducbible constitutively active version of HSF1 (cHSF1). This cell line was treated with 1ug/mL dox or vehicle (water) for 18 hours (in biological quadruplicate) to modulate the proteostasis environment in a stress-independent manner.