Hyperthermia stimulates HIV-1 replication.
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.
Institut Pasteur, Unité Virus et Immunité, Département de Virologie, Paris, France.
Ferdinand
F
Roesch
Oussama
O
Meziane
Anna
A
Kula
Sébastien
S
Nisole
Françoise
F
Porrot
Ian
I
Anderson
Fabrizio
F
Mammano
Ariberto
A
Fassati
Alessandro
A
Marcello
Monsef
M
Benkirane
Olivier
O
Schwartz
D016227:Benzoquinones / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D005334:Fever / Q000503:physiopathology*; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D019169:Jurkat Cells; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D054322:tat Gene Products, Human Immunodeficiency Virus; C112765:tanespimycin