Introduction Viral infection is one of the triggers to heat shock response which is an evolutionarily conserved cell protection mechanism in eukaryotic cells and is closely related to the key transcriptional factor heat shock factor 1 (HSF1). It is generally recognized that HSF1 and its downstream factors especially heat shock proteins play extensive roles in viral infection-associated immune response, cell death, and tissue injury. They work constructively in cell development, differentiation and aging in non-pathological conditions, and work inductively in cell stresses from external environment, cancer development, drug resistance and neurodegenerative diseases. In addition, HSF1 and its downstream factors were reported to extensively participate in HIV infection, propagation, latency reversing, and associated inflammatory response. Understanding the mechanism of HSF1 in both physiological and pathological conditions is important to elucidate the role of proteostasis in the action of protein machine in eukaryotic cells.