Fever onset is correlated with viremia in dengue virus (DENV) patients. Heat shock factor 1 (HSF1), a heat stress response host transcription factor, plays a crucial role in regulating multiple cellular functions, as well as the onset of infectious diseases. This study evaluated the role of HSF1 in DENV replication as a means of regulating DENV infection in vitro and in vivo. DENV infection activated HSF1 in both Ca²⁺ and protein kinase A-dependent manners. Inhibiting HSF1 effectively reduced DENV replication, not only in THP-1 cells but also in primary human monocytes. Activated HSF1 contributed to DENV replication by upregulating autophagy-related protein (Atg) 7, as autophagy is crucial for virus replication. Heat stress also activated HSF1, which in turn facilitated DENV replication. Activated HSF1, the increased Atg7, and autophagic induction were founded in the DENV-infected brains and pharmacologically inhibiting HSF1 reduced autophagy, viral protein expression, neuropathy, and mortality. These results provide new insight into HSF1 as a novel host factor for DENV infection through its role in facilitating autophagy-regulated viral replication in the brains.

登革热病毒（DENV）患者的发烧与病毒血症相关。热休克因子1（HSF1）是一种热应激反应宿主转录因子，在调节多种细胞功能以及感染性疾病的发作中起着至关重要的作用。本研究评价作为调节DENV感染的一种手段HSF1在DENV复制中的作用的体外和体内。DENV感染激活了Ca ^2+中的HSF1和蛋白激酶A依赖性方式。抑制HSF1不仅在THP-1细胞中而且在原代人单核细胞中均有效地减少了DENV复制。激活的HSF1通过上调自噬相关蛋白（Atg）7来促进DENV复制，因为自噬对于病毒复制至关重要。热应激还激活了HSF1，进而促进了DENV复制。在被DENV感染的大脑中发现了活化的HSF1，增加的Atg7和自噬诱导作用，并且在药理学上抑制了HSF1降低了自噬，病毒蛋白表达，神经病和死亡率。这些结果通过其在脑中促进自噬调节病毒复制的作用，为HSF1作为DENV感染的新型宿主因子提供了新的见解。