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Inhibition of Both HIV-1 Reverse Transcription and Gene Expression by a Cyclic Peptide that Binds the Tat-Transactivating Response Element (TAR) RNA

Figure 2

Testing the susceptibility of HIV-1 to inhibition by Tat peptidomimetics.

(A) Comparison of the relative inhibition of the HIV-1 NL4-3 laboratory strain by three lead Tat peptidomimetics. Virus production in cell free supernatant was measured using an endogenous RT assay. (B) The concentration for 50% inhibition (IC50) of HIV-1 NL4-3 was calculated for the lead Tat peptidomimetics and for the reference antiretroviral, 3TC. (C) Cell penetration (hT4R5 fibroblasts) and nuclear localization of fluorescein-labeled L-51 peptide analyzed by confocal microscopy. (D) L-50 inhibition of viral replication of three primary CCR5-tropic HIV-1 isolates measured in U87.CD4.CCR5 cells (A1 is the subtype A Rawandan isolate A1-92RW009, B5 is the subtype B isolate B5-91US056 from the USA and C5 is the subtype C isolate C5-97ZA003 from South Africa) and of CXCR4-tropic strains (D1 is the Ugandan subtype D isolate D1-92UG021, E6 is the subtype A/E circulating recombinant isolate CRF01_AE from Thailand) as well as the laboratory strain HIV-1NL4-3 measured in U87.CD4.CXCR4 cell cultures. The IC50 values for L50 and 3TC were calculated from drug susceptibility curves (Figure S1). (E) Inhibition of HIV NL4-3 was also measure in human peripheral blood mononuclear cells stimulated with PHA/IL-2. The nucleoside RT inhibitor, 3TC or the non-nucleoside RT inhibitor, nevirapine (NVP) were used as controls. Virus production was measured at 8 and 10 days post-infection by the RT activity in the supernatant (cpm/mL).

Figure 2

doi: https://doi.org/10.1371/journal.ppat.1002038.g002