AIDSWEEKLY Plus; Monday, November 28, 2005
Staff Medical Writers

"Patients infected with the human immunodeficiency virus (HIV), and other mammals infected with related lentiviruses, exhibit fatigue, altered sleep patterns, and abnormal circadian rhythms. A circadian clock in the hypothalamic suprachiasmatic nucleus (SCN) temporally regulates these functions in mammals," investigators in the United States report.

"We found that a secretary HIV transcription factor, transactivator of transcription (Tat), resets the murine circadian clock, in vitro and in vivo, at clinically relevant concentrations (EC₅₀=0.31 nM).

"This effect of Tat occurs only during the subjective night, when N-methyl-D-aspartate (NMDA) receptor [D-2-amino-5-phosphonovaleric acid (0.1 mM)] and nitric oxide synthase (N-G-nitro-L-arginine methyl ester, 0.1 mM) inhibitors block Tat-induced phase shifts," wrote J.P. Clark and colleagues at East Carolina University.

"Whole cell recordings of SCN neurons within the brain slice revealed that Tat did not activate NMDA receptors directly but potentiated NMDA receptor currents through the enhancement of glutamate release.

"Consistent with this presynaptic mechanism," the authors continued, "inhibitors of neurotransmission block Tat-induced phase shifts, such as tetrodotoxin (1 mc M), tetanus toxin (1 mcM), P/Q/N type-calcium channel blockers (1 mcM omega-agatoxin IVA and 1 mcM omega-conotoxin GIVA) and bafilomycin A(1) (1 mcM)."

"Thus, the effect of Tat on the SCN may underlie lentiviral circadian rhythm dysfunction by operating as a disease-dependent modulator of light entrainment through the enhancement of excitatory neurotransmission," suggested Clark.

Clark and colleagues published their study in American Journal of Physiology - Regulatory Integrative and Comparative Physiology (HIV protein, transactivator of transcription, alters circadian rhythms through the light entrainment pathway. Am J Physiol Regul Integr Comp Physiol. 2005 Sep;289(3):R656-62.

For additional information, contact J.M. Ding, E Carolina University, Brody School of Medicine, Dept. Physiol, 600 Moye Blvd., Greenville, NC 27858, USA.

The publisher of the American Journal of Physiology - Regulatory Integrative and Comparative Physiology can be contacted at: American Physiological Society, 9650 Rockville Pike, Bethesda, MD 20814, USA.

Keywords: Greenville, North Carolina, United States, HIV/AIDS, Circadian Clock, HIV Tat, Neurotransmission, Fatigue, Sleep Patterns, Circadian Rhythms.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Clark JP 3rd, Sampair CS, Kofuji P, et al., "HIV protein, transactivator of transcription, alters circadian rhythms through the light entrainment pathway", Am J Physiol Regul Integr Comp Physiol. 2005 Sep;289(3):R656-62.

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