Hyperthermia Stimulates HIV-1 Replication

PLoS Pathogens

Françoise Porrot¹  Alessandro Marcello²  Oussama Meziane²  Olivier Schwartz³  Ferdinand Roesch⁴  Ariberto Fassati⁴  Fabrizio Mammano⁵  Sébastien Nisole⁶  Ian Anderson⁷  Anna Kula⁸  Monsef Benkirane⁹ 

[1] CNRS, UPR1142, Montpellier, France;CNRS, URA3015, Paris, France;INSERM U941, Hôpital Saint Louis, Paris, France;Institut Pasteur, Unité Virus et Immunité, Département de Virologie, Paris, France;Institut Pasteur, Unité de Virologie Moléculaire et Vaccinologie, Paris, France;Institut de Génétique Humaine, Laboratoire de Virologie Moléculaire, Montpellier, France;Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy;Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France;Wohl Virion Centre, Division of Infection and Immunity, MRC Centre for Medical & Molecular Virology, University College London, London, United Kingdom

关键词: HIV-1;    Hyperthermia;    Viral replication;    T cells;    Fevers;    Cloning;    Flow cytometry;    HIV;   

DOI  :  10.1371/journal.ppat.1002792

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY