The activity of
Topoisomerase II alpha and beta
isoforms is tightly regulated during different phases of cell cycle. In the present study, the action of
anti-inflammatory agents,
nordihydroguaretic acid (NDGA) is analyzed in HIV-1 infected CXCR4(+), CCR5(+) and CD4(-) SK-N-SH
neuroblastoma, CXCR4(+), CCR5(+) and CD4(-) 1321N1
astrocytoma and CXCR4(+), CCR5(+/-) and CD4(-) GO-G-CCM
glioblastoma cell lines. In SK-N-SH and 1321N1 the expression of
Topoisomerase II alpha is concomitant with that of LOX-5 and is highly sensitive to NDGA, while the
Topoisomerase II beta is expressed along with
TNFalpha and exhibits low sensitivity to NDGA, suggesting distinct pathways of regulation for the two
isoforms. HIV-1
infection in these cells enhanced the expression of
Topo II alpha and beta. Further, the regulation of
Topo II beta and
TNFalpha in infected and uninfected SK cells is distinctly different. HIV-1 gp120 derived
peptides could block HIV-1 mediated
inflammation and
Topoisomerase II alpha and beta expression, suggesting the viral mediated response. A combination of NDGA, gp-120 derived
peptides and AZT has completely blocked the viral replication, suggesting the enhancement of potency of AZT under the suppression of inflammatory response. In contrast, the expression of
Topo II alpha and beta was stimulated by NDGA in GO-G-CCM cells showing distinct regulatory pathway in these cells that was resistant to HIV-1
infection. This suggests the requirement of inflammatory response for productive
viral infection. In summary, an induction of co-receptor mediated inflammatory response can distinctly enhance regulated expression of the cellular
Topo II alpha and beta and promote productive
infection in neurons and astrocytes.