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Open AccessArticle

Extended Interactions between HIV-1 Viral RNA and tRNALys3 Are Important to Maintain Viral RNA Integrity

Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(1), 58; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010058
Received: 6 November 2020 / Revised: 9 December 2020 / Accepted: 19 December 2020 / Published: 23 December 2020
(This article belongs to the Special Issue Virus Replication)
The reverse transcription of the human immunodeficiency virus 1 (HIV-1) initiates upon annealing of the 3′-18-nt of tRNALys3 onto the primer binding site (PBS) in viral RNA (vRNA). Additional intermolecular interactions between tRNALys3 and vRNA have been reported, but their functions remain unclear. Here, we show that abolishing one potential interaction, the A-rich loop: tRNALys3 anticodon interaction in the HIV-1 MAL strain, led to a decrease in viral infectivity and reduced the synthesis of reverse transcription products in newly infected cells. In vitro biophysical and functional experiments revealed that disruption of the extended interaction resulted in an increased affinity for reverse transcriptase (RT) and enhanced primer extension efficiency. In the absence of deoxyribose nucleoside triphosphates (dNTPs), vRNA was degraded by the RNaseH activity of RT, and the degradation rate was slower in the complex with the extended interaction. Consistently, the loss of vRNA integrity was detected in virions containing A-rich loop mutations. Similar results were observed in the HIV-1 NL4.3 strain, and we show that the nucleocapsid (NC) protein is necessary to promote the extended vRNA: tRNALys3 interactions in vitro. In summary, our data revealed that the additional intermolecular interaction between tRNALys3 and vRNA is likely a conserved mechanism among various HIV-1 strains and protects the vRNA from RNaseH degradation in mature virions. View Full-Text
Keywords: HIV-1 PBS; tRNALys3; reverse transcription; degradation; genomic RNA integrity HIV-1 PBS; tRNALys3; reverse transcription; degradation; genomic RNA integrity
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MDPI and ACS Style

Gremminger, T.; Song, Z.; Ji, J.; Foster, A.; Weng, K.; Heng, X. Extended Interactions between HIV-1 Viral RNA and tRNALys3 Are Important to Maintain Viral RNA Integrity. Int. J. Mol. Sci. 2021, 22, 58. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010058

AMA Style

Gremminger T, Song Z, Ji J, Foster A, Weng K, Heng X. Extended Interactions between HIV-1 Viral RNA and tRNALys3 Are Important to Maintain Viral RNA Integrity. International Journal of Molecular Sciences. 2021; 22(1):58. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010058

Chicago/Turabian Style

Gremminger, Thomas; Song, Zhenwei; Ji, Juan; Foster, Avery; Weng, Kexin; Heng, Xiao. 2021. "Extended Interactions between HIV-1 Viral RNA and tRNALys3 Are Important to Maintain Viral RNA Integrity" Int. J. Mol. Sci. 22, no. 1: 58. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010058

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