TY - JOUR
T1 - The Landscape of Persistent Viral Genomes in ART-Treated SIV, SHIV, and HIV-2 Infections
AU - Bender, Alexandra M.
AU - Simonetti, Francesco R.
AU - Kumar, Mithra R.
AU - Fray, Emily J.
AU - Bruner, Katherine M.
AU - Timmons, Andrew E.
AU - Tai, Katherine Y.
AU - Jenike, Katharine M.
AU - Antar, Annukka A.R.
AU - Liu, Po Ting
AU - Ho, Ya Chi
AU - Raugi, Dana N.
AU - Seydi, Moussa
AU - Gottlieb, Geoffrey S.
AU - Okoye, Afam A.
AU - Del Prete, Gregory Q.
AU - Picker, Louis J.
AU - Mankowski, Joseph L.
AU - Lifson, Jeffrey D.
AU - Siliciano, Janet D.
AU - Laird, Greg M.
AU - Barouch, D. H.
AU - Clements, Janice E.
AU - Siliciano, Robert F.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/7/10
Y1 - 2019/7/10
N2 - 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. Understanding the proviral landscape in ART-treated non-human primates (NHP) is crucial before using them to test HIV cure strategies. Bender et al. report that while most proviruses persisting in ART-treated SIV-infected NHPs are defective, there is a significantly higher fraction of intact genomes compared to ART-treated HIV-1-infected humans.
AB - 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. Understanding the proviral landscape in ART-treated non-human primates (NHP) is crucial before using them to test HIV cure strategies. Bender et al. report that while most proviruses persisting in ART-treated SIV-infected NHPs are defective, there is a significantly higher fraction of intact genomes compared to ART-treated HIV-1-infected humans.
KW - HIV-2
KW - SHIV
KW - SIV
KW - clonal expansion
KW - defective provirus
KW - latent reservoir
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U2 - 10.1016/j.chom.2019.06.005
DO - 10.1016/j.chom.2019.06.005
M3 - Article
C2 - 31295427
AN - SCOPUS:85068104375
SN - 1931-3128
VL - 26
SP - 73-85.e4
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 1
ER -