The expression of P-glycoprotein and cellular kinases is modulated at the transcriptional level by infection and highly active antiretroviral therapy in a primate model of AIDS.
The beneficial effects of highly active antiretroviral therapy (HAART) in HIV-infected patients may be limited by inadequate compliance and viral resistance, but also by host cell factors, such as P-glycoprotein (P-gp) and intracellular kinases involved in the phosphorylation of nucleoside reverse transcriptase inhibitors. We investigated the effects of infection and HAART (zidovudine [AZT], lamivudine [3TC], and indinavir [IDV] on the expression of P-gp and cell kinases involved in the phosphorylation of AZT and 3TC in SHIV89.6P-infected cynomolgus macaques. Under unstimulated conditions, we observed a decrease in P-gp mRNA levels in the peripheral blood and lymph node mononuclear cells of infected macaques, which was accentuated by HAART. SHIV infection also resulted in the overexpression of thymidine kinase mRNA, which was abolished by HAART. In conclusion, retroviral infection and HAART modulate in vivo at the transcriptional level the expression of host cell factors that may affect the efficacy of HAART.
Jorajuria
Sylvie
S
CEA, Service de Neurovirologie, DRM/DSV, CRSSA, EPHE, IPSC, 92265 Fontenay-aux-Roses, France.
Clayette
Pascal
P
Dereuddre-Bosquet
Nathalie
N
Benlhassan-Chahour
Kadija
K
Thiébot
Hugues
H
Vaslin
Bruno
B
Le Grand
Roger
R
Dormont
Dominique
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D018655:Lymphocyte Count; D008252:Macaca fascicularis; D012367:RNA, Viral / Q000097:blood; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012367:RNA, Viral; D013937:Thymidine Kinase