Liver X receptor agonist inhibits HIV-1 replication and prevents HIV-induced reduction of plasma HDL in humanized mouse model of HIV infection.
HIV-infected subjects are at high risk of developing atherosclerosis, in part due to virus-induced impairment of HDL metabolism. Here, using as a model of HIV infection the NOD.Cg-Prkdc(scid)IL2rg(tm1Wjl)/SzJ (NSG) mice humanized by human stem cell transplantation, we demonstrate that LXR agonist TO901317 potently reduces viral replication and prevents HIV-induced reduction of plasma HDL. These results establish that humanized mice can be used to investigate the mechanisms of HIV-induced impairment of HDL formation, a major feature of dyslipidemia associated with HIV-1 infection, and show potential benefits of developing LXR agonists for treatment of HIV-associated cardio-vascular disease.
The George Washington University, Washington, DC, USA.
Larisa
L
Dubrovsky
Rachel
R
Van Duyne
Svetlana
S
Senina
Irene
I
Guendel
Tatiana
T
Pushkarsky
Dmitri
D
Sviridov
Fatah
F
Kashanchi
Michael
M
Bukrinsky
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D015658:HIV Infections / Q000097:blood* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000097:blood*; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000819:agonists*; D033581:Stem Cell Transplantation; D013449:Sulfonamides / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D000924:Anticholesteremic Agents; D006845:Hydrocarbons, Fluorinated; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides