HIV-2 induces NF-kappaB activation and cyclooxygenase-2 expression in human astroglial cells.
HIV-2 invades CNS and causes neurological disease as well as HIV-1 does. Induction of COX-2 in CNS of HIV-1 infected people has been proposed as a cause of cognitive impairment, so we tested whether HIV-2 may cause damage by a similar mechanism. COX-2 mRNA and protein expression were induced in human astrocytes upon interaction with HIV-2, being this induction abrogated by CXCR4 antagonists. HIV-2 induced COX-2 promoter transcription and deletion of the two NF-kappaB binding sites of the promoter abrogated this induction. Neither AP-1 nor NFAT seem to be involved in COX-2 transcriptional activation. Overexpression of IkappaBalpha completely abrogated COX-2 induction, and transfection of p65/relA NF-kappaB induced COX-2 transcription. Interestingly, HIV-2 activated NF-kappaB by inducing p65/relA transactivating activity through Ser536 phosphorylation. Moreover, the astrocyte activation induced by HIV-2 was abrogated by different COX inhibitors. In summary, HIV-2 induces COX-2 in human astrocytes depending on CXCR4 coreceptor.
Alvarez
Susana
S
Centro de Biología Molecular, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Blanco
Almudena
A
Kern
Florian
F
Fresno
Manuel
M
Muñoz-Fernández
Ma Angeles
MA