Redox imbalance and its control in HIV infection.
Human immunodeficiency virus (HIV)-infected individuals are suffering from systemic oxidative stress. Reactive oxygen species act as second messengers for the activation of nuclear factor-kappaB (NF-kappaB), which augments the replication of HIV. Intracellular levels of glutathione (GSH), a major cytosolic antioxidant, in T cells decrease during the disease progression. Another redox-regulating molecule, thioredoxin (TRX), is also transiently down-regulated in the cells by acute HIV infection. In contrast, plasma levels of TRX are elevated in the late stage of HIV infection. Intracellular GSH and plasma TRX can be biomarkers to predict the prognosis of the disease. N-Acetylcysteine (NAC), a prodrug of cysteine that is necessary for GSH synthesis, has been used for HIV infection to prevent the activation of NF-kappaB and the replication of HIV. NAC shows some beneficial effects for HIV-infected individuals, although the intracellular GSH levels in lymphocytes are not significantly restored. The control of imbalanced redox status by antioxidants may be beneficial for the quality of life in HIV infection even in the era after the effective therapy with protease inhibitors has been applied. Redox control will be an important therapeutic strategy for oxidative stress-associated disorders including HIV infection.
Nakamura
Hajime
H
Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Shogin-Kawaharacho, Sakyo, Kyoto 606-8507, Japan. hnakamur@virus.kyoto-u.ac.jp
Masutani
Hiroshi
H
Yodoi
Junji
J
D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011355:Prodrugs / Q000378:metabolism; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements; D013879:Thioredoxins / Q000097:blood
D000975:Antioxidants; D011355:Prodrugs; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D005978:Glutathione