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

Author:

Liu, Yang

Chen, Jianbo

Nikolaitchik, Olga

Desimmie, Belete

Busan, Steven

Pathak, Vinay

Weeks, Kevin M

Hu, Wei-Shau
Author Address

Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Viral Mutation Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA., Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA., Viral Recombination Section, HIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: Wei-Shau.Hu@nih.gov.,

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. Copyright © 2017. Published by Elsevier Inc.

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