Production of HIV-1 MRNA Is Modulated by Natural Nucleotide Variations and SLSA1 RNA Structure in SA1D2prox Genomic Region

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2018 Jan 13

PMID 29326677

Citations 6

Authors

Masako Nomaguchi

Naoya Doi

Tomoya Yoshida

Takaaki Koma

Shun Adachi

Hirotaka Ode

Yasumasa Iwatani

Masaru Yokoyama

Hironori Sato

Akio Adachi

Affiliations

Soon will be listed here.

Abstract

Genomic RNA of HIV-1 contains localized structures critical for viral replication. Its structural analysis has demonstrated a stem-loop structure, SLSA1, in a nearby region of HIV-1 genomic splicing acceptor 1 (SA1). We have previously shown that the expression level of mRNA is considerably altered by some natural single-nucleotide variations (nSNVs) clustering in SLSA1 structure. In this study, besides eleven nSNVs previously identified by us, we totally found nine new nSNVs in the SLSA1-containing sequence from SA1, splicing donor 2, and through to the start codon of Vif that significantly affect the mRNA level, and designated the sequence SA1D2prox (142 nucleotides for HIV-1 NL4-3). We then examined by extensive variant and mutagenesis analyses how SA1D2prox sequence and SLSA1 secondary structure are related to mRNA level. While the secondary structure and stability of SLSA1 was largely changed by nSNVs and artificial mutations introduced to restore the original NL4-3 form from altered ones by nSNVs, no clear association of the two SLSA1 properties with mRNA level was observed. In contrast, when naturally occurring SA1D2prox sequences that contain multiple nSNVs were examined, we attained significant inverse correlation between the level and SLSA1 stability. These results may suggest that SA1D2prox sequence adapts over time, and also that the altered SA1D2prox sequence, SLSA1 stability, and level are mutually related. In total, we show here that the entire SA1D2prox sequence and SLSA1 stability critically contribute to the modulation of mRNA level.

Citing Articles

Involvement of a Rarely Used Splicing SD2b Site in the Regulation of HIV-1 mRNA Production as Revealed by a Growth-Adaptive Mutation.

Koma T, Doi N, Le B, Kondo T, Ishizue M, Tokaji C Viruses. 2023; 15(12).

PMID: 38140666 PMC: 10747208. DOI: 10.3390/v15122424.

The Expression Level of HIV-1 Vif Is Optimized by Nucleotide Changes in the Genomic SA1D2prox Region during the Viral Adaptation Process.

Koma T, Doi N, Takemoto M, Watanabe K, Yamamoto H, Nakashima S Viruses. 2021; 13(10).

PMID: 34696508 PMC: 8537775. DOI: 10.3390/v13102079.

Commentary: Derivation of Simian Tropic HIV-1 Infectious Clone Reveals Virus Adaptation to a New Host.

Adachi A, Koma T, Doi N, Nomaguchi M Front Cell Infect Microbiol. 2020; 10:235.

PMID: 32500043 PMC: 7243179. DOI: 10.3389/fcimb.2020.00235.

Grand Challenge in Human/Animal Virology: Unseen, Smallest Replicative Entities Shape the Whole Globe.

Adachi A Front Microbiol. 2020; 11:431.

PMID: 32256480 PMC: 7093566. DOI: 10.3389/fmicb.2020.00431.

Expression Level of HIV-1 Vif Can Be Fluctuated by Natural Nucleotide Variations in the -Coding and Regulatory SA1D2prox Sequences of the Proviral Genome.

Doi N, Koma T, Adachi A, Nomaguchi M Front Microbiol. 2019; 10:2758.

PMID: 31849897 PMC: 6893887. DOI: 10.3389/fmicb.2019.02758.

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