[PDF][PDF] The landscape of persistent viral genomes in ART-treated SIV, SHIV, and HIV-2 infections

AM Bender, FR Simonetti, MR Kumar, EJ Fray… - Cell host & …, 2019 - cell.com
AM Bender, FR Simonetti, MR Kumar, EJ Fray, KM Bruner, AE Timmons, KY Tai, KM Jenike
Cell host & microbe, 2019cell.com
Evaluation of HIV cure strategies is complicated by defective proviruses that persist in ART-
treated patients but are irrelevant to cure. Non-human primates (NHP) are essential for
testing cure strategies. However, the persisting proviral landscape in ART-treated NHPs is
uncharacterized. Here, we describe viral genomes persisting in ART-treated, simian
immunodeficiency virus (SIV)-infected NHPs, simian-human immunodeficiency virus (SHIV)-
infected NHPs, and humans infected with HIV-2, an SIV-related virus. The landscapes of …
Summary
Evaluation of HIV cure strategies is complicated by defective proviruses that persist in ART-treated patients but are irrelevant to cure. Non-human primates (NHP) are essential for testing cure strategies. However, the persisting proviral landscape in ART-treated NHPs is uncharacterized. Here, we describe viral genomes persisting in ART-treated, simian immunodeficiency virus (SIV)-infected NHPs, simian-human immunodeficiency virus (SHIV)-infected NHPs, and humans infected with HIV-2, an SIV-related virus. The landscapes of persisting SIV, SHIV, and HIV-2 genomes are also dominated by defective sequences. However, there was a significantly higher fraction of intact SIV proviral genomes compared to ART-treated HIV-1 or HIV-2 infected humans. Compared to humans with HIV-1, SIV-infected NHPs had more hypermutated genomes, a relative paucity of clonal SIV sequences, and a lower frequency of deleted genomes. Finally, we report an assay for measuring intact SIV genomes which may have value in cure research.
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