Hyperthermia Stimulates HIV-1 Replication

• DOI: 10.1371/journal.ppat.1002792
• Publication Date: 2012-07-13T19:51:50Z
• Authors: Ferdinand Roesch; Oussama Meziane; Anna Kula; Sébastien Nisole; Françoise Porrot; Ian Anderson; Fabrizio Mammano; Ariberto Fassati; Alessandro Marcello; Monsef Benkirane; Olivier Schwartz
• Keywords: CD4-Positive T-Lymphocytes; Gene Expression Regulation, Viral; Transcriptional Activation; Hot Temperature; Fever; QH301-705.5; Lactams, Macrocyclic; HIV Infections; [SDV.GEN] Life Sciences [q-bio]/Genetics; Virus Replication; Jurkat Cells; 03 medical and health sciences; Benzoquinones; Humans; HSP90 Heat-Shock Proteins; Biology (General); Promoter Regions, Genetic; HIV Long Terminal Repeat; [SDV.GEN]Life Sciences [q-bio]/Genetics; 0303 health sciences; RC581-607; Virus Latency; 3. Good health; HIV-1; Virus Activation; tat Gene Products, Human Immunodeficiency Virus; Immunologic diseases. Allergy; Research Article; HeLa Cells

HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C) on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C) increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.