The HIV 5' Gag Region Displays a Specific Nucleotide Bias Regulating Viral Splicing and Infectivity

Grewe B, Vogt C, Horstkötter T, Tippler B, Xiao H, Müller B, Überla K, Wagner R, Asbach B, Bohne J (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Viruses MDPI

Book Volume: 13

Journal Issue: 6

DOI: 10.3390/v13060997

Abstract

Alternative splicing and the expression of intron-containing mRNAs is one hallmark of HIV gene expression. To facilitate the otherwise hampered nuclear export of non-fully processed mRNAs, HIV encodes the Rev protein, which recognizes its intronic response element and fuels the HIV RNAs into the CRM-1-dependent nuclear protein export pathway. Both alternative splicing and Rev-dependency are regulated by the primary HIV RNA sequence. Here, we show that these processes are extremely sensitive to sequence alterations in the 5'coding region of the HIV genomic RNA. Increasing the GC content by insertion of either GFP or silent mutations activates a cryptic splice donor site in gag, entirely deregulates the viral splicing pattern, and lowers infectivity. Interestingly, an adaptation of the inserted GFP sequence toward an HIV-like nucleotide bias reversed these phenotypes completely. Of note, the adaptation yielded completely different primary sequences although encoding the same amino acids. Thus, the phenotypes solely depend on the nucleotide composition of the two GFP versions. This is a strong indication of an HIV-specific mRNP code in the 5' gag region wherein the primary RNA sequence bias creates motifs for RNA-binding proteins and controls the fate of the HIV-RNA in terms of viral gene expression and infectivity.

Authors with CRIS profile

Han Xiao Institute of Clinical and Molecular Virology Klaus Überla Lehrstuhl für Klinische und Molekulare Virologie

Involved external institutions

Ruhr-Universität Bochum (RUB) DE Germany (DE) Universität Regensburg DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE)

How to cite

APA:

Grewe, B., Vogt, C., Horstkötter, T., Tippler, B., Xiao, H., Müller, B.,... Bohne, J. (2021). The HIV 5' Gag Region Displays a Specific Nucleotide Bias Regulating Viral Splicing and Infectivity. Viruses, 13(6). https://doi.org/10.3390/v13060997

MLA:

Grewe, Bastian, et al. "The HIV 5' Gag Region Displays a Specific Nucleotide Bias Regulating Viral Splicing and Infectivity." Viruses 13.6 (2021).

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