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Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape.

Cell Host Microbe. 2017; 
Pollack RA, Jones RB, Pertea M, Bruner KM, Martin AR, Thomas AS, Capoferri AA, Beg SA, Huang SH, Karandish S, Hao H, Halper-Stromberg E, Yong PC, Kovacs C, Benko E, Siliciano RF, Ho YC.
Products/Services Used Details Operation
PCR Cloning and Subcloning Defective proviral plasmids were reconstructed into the NL4-3 reference plasmid using de novo genome synthesis to avoid cloning of PCR-induced errors (Genscript) (Ho et al. Get A Quote

摘要

Despite antiretroviral therapy, HIV-1 persists in memory CD4+ T cells, creating a barrier to cure. The majority of HIV-1 proviruses are defective and considered clinically irrelevant. Using cells from HIV-1-infected individuals and reconstructed patient-derived defective proviruses, we show that defective proviruses can be transcribed into RNAs that are spliced and translated. Proviruses with defective major splice donors (MSDs) can activate novel splice sites to produce HIV-1 transcripts, and cells with these proviruses can be recognized by HIV-1-specific cytotoxic T lymphocytes (CTLs). Further, cells with proviruses containing lethal mutations upstream of CTL epitopes can also be recognized by CTLs, potentia... More

关键词

APOBEC-mediated G-to-A hypermutations; HIV-1 cure; HIV-1 latent reservoir; HIV-1 proviral landscape; alternative splicing; cell-associated HIV-1 RNA; cold-target inhibition; cytotoxic T lymphocytes; defective HIV-1 proviruses; defective ribosomal product