Human immunodeficiency virus type 1 clade B and C gp120 differentially induce neurotoxin arachidonic acid in human astrocytes: implications for neuroAIDS

• Published in: Journal of neurovirology 2011-06, Vol.17 (3), p.230-238
• Main Authors: Samikkannu, Thangavel, Agudelo, Marisela, Gandhi, Nimisha, Reddy, Pichili V. B., Saiyed, Zainulabedin M., Nwankwo, Donald, Nair, Madhavan P. N.
• Format: Article
• Language: English
• Subjects: AIDS Dementia Complex - metabolism; AIDS Dementia Complex - pathology; Arachidonic acid; Arachidonic Acid - biosynthesis; Astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Astrocytes - virology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cell Culture Techniques; Cells, Cultured; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Dementia disorders; Dinoprostone - biosynthesis; Down-Regulation; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Glutamine; Glutamine - biosynthesis; Glycoprotein gp120; HIV Envelope Protein gp120 - metabolism; HIV Envelope Protein gp120 - pharmacology; HIV Infections - metabolism; HIV Infections - pathology; HIV-1 - physiology; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunology; Infectious Diseases; Medical sciences; N-Methyl-D-aspartic acid receptors; Neurology; Neuropathogenesis; Neuropathology; Neurosciences; Neurotoxins; Neurotoxins - biosynthesis; Prostaglandin E2; Protein Isoforms - metabolism; Protein Isoforms - pharmacology; Receptors, N-Methyl-D-Aspartate - biosynthesis; Receptors, Thromboxane A2, Prostaglandin H2 - biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; thromboxane A2 receptors; Up-Regulation; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral diseases of the nervous system; Virology
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1007/s13365-011-0026-5

HIV-1 clades (subtypes) differentially contribute to the neuropathogenesis of HIV-associated dementia (HAD) in neuroAIDS. HIV-1 envelop protein, gp120, plays a major role in neuronal function. It is not well understood how these HIV-1 clades exert these neuropathogenic differences. The N -methyl- d -aspartate (NMDA) receptor-reduced glutamine synthesis could lead to secretion of neurotoxins such as arachidonic acid (AA) which plays a significant role in the neuropathogenic mechanisms in neuroAIDS. We hypothesize that clade B and C gp120 proteins exert differential effects on human primary astrocytes by production of the neurotoxin arachidonic acid. Our results indicate that clade B gp120 significantly downregulated NMDA receptor gene and protein expression, and level of glutamine while increasing expression of prostaglandin E2 (PGE 2 ) and thromboxane A2 receptor (TBXA 2 R) compared to HIV-1 clade C gp120 protein. Thus, our studies for the first time demonstrate that HIV-1 clade B-gp120 protein appears to induce higher levels of expression of the neuropathogenic molecule cyclooxygenase-2 (COX-2)-mediated arachidonic acid by-products, PGE 2 , and TBXA 2 R compared to HIV-1 clade C gp120 protein. These studies suggest that HIV-1 clade B and C gp120 proteins may play a differential role in the neuropathogenesis of HAD in neuroAIDS.