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Fig. 4 | Retrovirology

Fig. 4

From: NNRTI-induced HIV-1 protease-mediated cytotoxicity induces rapid death of CD4 T cells during productive infection and latency reversal

Fig. 4

NNRTI-induced killing is sensitive to HIV-1 mutations leading to both NNRTI and PI resistance. a, b Cells were infected with single round GFP reporter virus containing or not the NNRTI resistant conferring RT K103N mutation. Cells were treated with the indicated dose of EFV and RPV on day 0 (a) or day 5 (b) and analyzed 5 days and 4 h later, respectively. The % of GFP+ cells within the live cells (defined by FSC and SSC), was normalized to the untreated condition for the corresponding virus (= 100%). c Inhibition NNRTI-induced killing of WT and PI resistant HIV-1 by PIs. Cells were infected with NL4-3 virus or patient isolated viruses containing a PI resistant PR. At 5 dpi cells were treated with RPV (1 μM) and the PR inhibitors IDV (1 μM), SQV (1 μM) or TPV (2 μM) and samples were collected 4 h later. Productively infected cells were identified by intracellular p24Gag staining within the live cells (defined by FSC and SSC). d NNRTI killing tested on a panel of transmitter/founder (TF) viruses. All the viruses were sensitive to NNRTI killing except pCH058 and pCH077. The percent of P24Gag+ cells was normalized to the untreated condition for each virus (= 100%). (*p < 0.0001: p-values were calculated, between RPV treatment and no treatment for each TF virus, with an unpaired two-tailed t-test). Cell death was assessed 4 h after NNRTI treatment. e NNRTI resistance-conferring RT mutations in bold red type identified in pCH058 and PCH077 via the Stanford University HIV Drug Resistance Database [49,50,51]

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