Abstract:
Latent HIV reservoirs in infected individuals prevent current treatment from eradicating
infection. Treatment strategies against latency involve adjuvants for viral reactivation which
exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated
from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in
the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs) of
infected patients on combination antiretroviral therapy (cART). The mechanism of viral reactivation
was determined through the compound’s effect on cytokine production, histone deacetylase
(HDAC) inhibition, and protein kinase C (PKC) activation. Cytotoxicity of the triterpenoids
was determined using a tetrazolium dye and flow cytometry. The isolated triterpene isomers,
3-hydroxy-4,6a,6b,11,12,14b-hexamethyl-1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydrop
icene-4,8a-dicarboxylic acid (HHODC), significantly (p < 0.05) induced HIV-1 expression in a
dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC also induced viral
expression in PBMCs of HIV-1 infected patients on cART. In addition, the compound up-regulated
the production of interleukin (IL)-2, IL-6, tumour necrosis factor (TNF)- , and interferon (IFN)-
but
had no effect on HDAC and PKC activity, suggesting cytokine upregulation as being involved in
latency activation. The observed in vitro reactivation of HIV-1 introduces the adjuvant potential of
HHODC for the first time here.
Description:
Supplementary Material: Figure S1: Effect of amyrin on HIV-1
expression, Figure S2: Effect of HHODC on HIV-1 PR, Figure S3a,b: Effects of HHODC on HDAC and PKC
activities, Figure S4: Effect of HHODC on the viability of PBMCs.
