Hyperthermia stimulates HIV-1 replication.

Ferdinand Roesch (1) , Oussama Meziane (2) , Anna Kula (3) , Sébastien Nisole (4) , Françoise Porrot (1) , Ian Anderson (5) , Fabrizio Mammano (6) , Ariberto Fassati (5) , Alessandro Marcello (7) , Monsef Benkirane (2) , Olivier Schwartz (1)

1 Virus et Immunité
2 IGH - Institut de génétique humaine
3 Laboratory of Molecular Virology
4 Virologie moléculaire et vaccinologie
5 Wohl Virion Centre, Division of Infection and Immunity
6 Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales
7 Laboratory of Molecular Virology

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.

Domaines: Génétique

Ferdinand Roesch, Oussama Meziane, Anna Kula, Sébastien Nisole, Françoise Porrot, et al.. Hyperthermia stimulates HIV-1 replication.. PLoS Pathogens, 2012, 8 (7), pp.e1002792. ⟨10.1371/journal.ppat.1002792⟩. ⟨hal-00723104⟩