HIV-1 RNAs whose transcription initiates from the third deoxyguanosine of GGG tract in the 5′ long terminal repeat serve as a dominant genome for efficient provirus DNA formation

Author:

Yoshida Takeshi12ORCID,Kasuya Yuho23,Yamamoto Hiroyuki24,Kawai Gota5,Hanaki Ken-ichi1,Matano Tetsuro267,Masuda Takao58

Affiliation:

1. Management Department of Biosafety, Laboratory Animal, and Pathogen Bank, National Institute of Infectious Diseases, Tokyo, Japan

2. AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan

3. Department of Molecular Virology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

4. Department of Biomedicine, University Hospital Basel, Basel, Switzerland

5. Department of Life Science, Faculty of Advanced Engineering, Chiba Institute of Technology, Chiba, Japan

6. Institute of Medical Science, The University of Tokyo, Tokyo, Japan

7. Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan

8. Graduate school of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

Abstract

Since the promoter for transcribing HIV-1 RNA is unique, all viral elements including genomic RNA and viral proteins have to be generated by the unique transcripts through ingenious mechanisms including RNA splicing and frameshifting during protein translation. Previous studies suggested a new mechanism for diversification of HIV-1 RNA functions by heterogeneous transcriptional initiation site usage; HIV-1 RNAs whose transcription initiates from a certain nucleotide were predominant in virus particles. In this study, we established two methods to analyze heterogenous transcriptional initiation site usage by HIV-1 during viral infection and showed that RNAs beginning with one guanosine (G1-form RNAs), whose transcription initiates from the third deoxyguanosine of the GGG tract in 5′ LTR, were primarily selected as viral genome in infectious particles and thus are used as a template to generate provirus for continuous replication. This study provides insights into the mechanism for diversification of unspliced RNA functions and requisites of lentivirus infectivity.

Funder

Japan Agency for Medical Research and Development

Takeda Science Foundation

Publisher

American Society for Microbiology

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Transcription start site choice regulates HIV-1 RNA conformation and function;Current Opinion in Structural Biology;2024-10

2. Role of RNA structural plasticity in modulating HIV-1 genome packaging and translation;Proceedings of the National Academy of Sciences;2024-08-07

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