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The roles of five conserved lentiviral RNA structures in HIV-1 replication.

The roles of five conserved lentiviral RNA structures in HIV-1 replication.
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Liu Y, Chen J, Nikolaitchik OA, Desimmie BA, Busan S, Pathak VK, Weeks KM, Hu WS,


Liu Y, Chen J, Nikolaitchik OA, Desimmie BA, Busan S, Pathak VK, Weeks KM, Hu WS, (click to view)

Liu Y, Chen J, Nikolaitchik OA, Desimmie BA, Busan S, Pathak VK, Weeks KM, Hu WS,

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Virology 2017 11 09514() 1-8 pii 10.1016/j.virol.2017.10.020

Abstract

The HIV-1 RNA genome contains complex structures with many structural elements playing regulatory roles during viral replication. A recent study has identified multiple RNA structures with unknown functions that are conserved among HIV-1 and two simian immunodeficiency viruses. To explore the roles of these conserved RNA structures, we introduced synonymous mutations into the HIV-1 genome to disrupt each structure. These mutants exhibited similar particle production, viral infectivity, and replication kinetics relative to the parent NL4-3 virus. However, when replicating in direct competition with the wild-type NL4-3 virus, mutations of RNA structures at inter-protein domain junctions can cause fitness defects. These findings reveal the ability of HIV-1 to tolerate changes in its sequences, even in apparently highly conserved structures, which permits high genetic diversity in HIV-1 population. Our results also suggest that some conserved RNA structures may function to fine-tune viral replication.

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