G-quadruplexes in genomes of viruses infecting eukaryotes or prokaryotes are under different selection pressures from hosts

Li, Zhen; Qian, Sheng Hu; Wang, Fan; Mohamed, Hany I.; Yang, Guang‐Fu; Chen, Zhenxia; Wei, Dengguo

doi:10.1016/j.jgg.2021.08.018

Cited by 8 publications

(6 citation statements)

References 60 publications

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“…All putative G4 sequences (PQSs) on both strands were predicted by quadpaser [ 11 ]. The detailed PQS information in viral genomes were uploaded to database Viral Putative G-quadruplex Database (ViPGD) ( http://jsjds.hzau.edu.cn/MBPC/ViPGD/index.php/home/index ) to facilitate users to visually browse or search PQSs in different viruses [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

“…A total of six PQSs were identified in the TMV genome (NC_001367.1), of which PQS1, PQS2, and PQS3 were located in the coding region of the replicase; PQS4 and PQS5 were in the coding region of the movement protein, and PQS6 was located in the coding region of the coat protein ( Fig 1 ). Pattern conservation, sequence conservation, and folding potential of PQSs were determined to evaluate the functional potential of PQSs in the genome ( Fig 1 and S2 Table ) [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

“…TMV, a model plant virus, has been widely used in virology study and antiviral agent discovery [13]. A total of six PQSs were identified in the TMV genome (NC_001367.1), of which PQS1, PQS2, and PQS3 were located in the coding region of the replicase; PQS4 and PQS5 were in the coding region of the movement protein, and PQS6 was located in the coding region of the coat protein ( [12].…”

Section: Identification Of G4-forming Sequences In Tmv Genomementioning

confidence: 99%

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G-quadruplex in the TMV Genome Regulates Viral Proliferation and Acts as Antiviral Target of Photodynamic Therapy

Xie,

Zhang,

Pei

et al. 2023

PLoS Pathog

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Plant viruses seriously disrupt crop growth and development, and classic protein-targeted antiviral drugs could not provide complete protection against them. It is urgent to develop antiviral compounds with novel targets. Photodynamic therapy shows potential in controlling agricultural pests, but nonselective damage from reactive oxygen species (ROS) unexpectedly affects healthy tissues. A G-quadruplex (G4)-forming sequence in the tobacco mosaic virus (TMV) genome was identified to interfere the RNA replication in vitro, and affect the proliferation of TMV in tobacco. N-methyl mesoporphyrin IX stabilizing the G4 structure exhibited inhibition against viral proliferation, which was comparable to the inhibition effect of ribavirin. This indicated that G4 could work as an antiviral target. The large conjugate planes shared by G4 ligands and photosensitizers (PSs) remind us that the PSs could work as antiviral agents by targeting G4 in the genome of TMV. Chlorin e6 (Ce6) was identified to stabilize the G4 structure in the dark and selectively cleave the G4 sequence by producing ROS upon LED-light irradiation, leading to 92.2% inhibition against TMV in vivo, which is higher than that of commercial ningnanmycin. The inhibition of Ce6 was lost against the mutant variants lacking the G4-forming sequence. These findings indicated that the G-quadruplex in the TMV genome worked as an important structural element regulating viral proliferation, and could act as the antiviral target of photodynamic therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Identification Of G4-forming Sequences In Tmv Genomementioning

confidence: 99%

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G-quadruplex in the TMV Genome Regulates Viral Proliferation and Acts as Antiviral Target of Photodynamic Therapy

Xie,

Zhang,

Pei

et al. 2023

PLoS Pathog

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“…G4 sequences with G-tracts of 2–4 base lengths can form G4 structures with 2–4 G-tetrad layers. Such a sequence feature is used to predict PQS [ 2 , 3 ] by four algorithms, including regular expression matching algorithms [ 4 , 5 ], scoring algorithms [ 6 , 7 ], sliding window algorithms [ 8 , 9 ], and machine learning algorithms [ 10 ]. The algorithms for G4 prediction have been continuously improved, which increases our understanding of eG4s, but the false positive rate of existing algorithms is still high, and so far no software can predict dynamic eG4s, which hinders the study of eG4 function.…”

Section: Introductionmentioning

confidence: 99%

In vivo dynamics and regulation of DNA G-quadruplex structures in mammals

et al. 2023

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G-quadruplex (G4) is a four-stranded helical DNA secondary structure formed by guanine-rich sequence folding, and G4 has been computationally predicted to exist in a wide range of species. Substantial evidence has supported the formation of endogenous G4 (eG4) in living cells and revealed its regulatory dynamics and critical roles in several important biological processes, making eG4 a regulator of gene expression perturbation and a promising therapeutic target in disease biology. Here, we reviewed the methods for prediction of potential G4 sequences (PQS) and detection of eG4s. We also highlighted the factors affecting the dynamics of eG4s and the effects of eG4 dynamics. Finally, we discussed the future applications of eG4 dynamics in disease therapy.

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“…G4s are thermodynamically stable and have much slower unfolding kinetics than other DNA hairpin structures ( Lane et al, 2008 ). Mounting evidence suggests their involvement in key biological processes, including transcription, replication, and regulation of gene expression, hence are of great therapeutic interest from a drug development perspective ( Rhodes and Lipps, 2015 ; Li et al, 2021 ). Targeting G4s has the edge over other DNA structures.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of G-Quadruplexes in African Swine Fever Virus Genome Reveals Potential Antiviral Targets by G-Quadruplex Stabilizers

et al. 2021

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African Swine Fever Virus (ASFV), a lethal hemorrhagic fever of the swine, poses a major threat to the world’s swine population and has so far resulted in devastating socio-economic consequences. The situation is further compounded by the lack of an approved vaccine or antiviral drug. Herein, we investigated a novel anti-ASFV approach by targeting G-Quadruplexes (G4s) in the viral genome. Bioinformatics analysis of putative G-quadruplex-forming sequences (PQSs) in the genome of ASFV BA71V strain revealed 317 PQSs on the forward strand and 322 PQSs on the reverse strand of the viral genome, translating to a density of 3.82 PQSs/kb covering 9.52% of the entire genome, which means that 85% of genes in the ASFV genome have at least 1 PQS on either strand. Biochemical characterization showed that 8 out of 13 conserved PQSs could form stable G4s in the presence of K+, and 4 of them could be stabilized by G4 ligands, N-Methyl Mesoporphyrin (NMM), and pyridostatin (PDS) in vitro. An enhanced green fluorescent protein (EGFP)-based reporter system revealed that the expression of two G4-containing genes, i.e., P1192R and D117L, could be significantly suppressed by NMM and PDS in 293T cells. In addition, a virus infection model showed that NMM could inhibit the replication of ASFV in Porcine Alveolar Macrophages (PAM) cells with an EC50 value of 1.16 μM. Altogether, the present study showed that functional PQSs existent in the promoters, CDS, 3′ and 5′ UTRs of the ASFV genome could be stabilized by G4 ligands, such as NMM and PDS, and could serve as potential targets for antivirals.

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G-quadruplexes in genomes of viruses infecting eukaryotes or prokaryotes are under different selection pressures from hosts

Cited by 8 publications

References 60 publications

G-quadruplex in the TMV Genome Regulates Viral Proliferation and Acts as Antiviral Target of Photodynamic Therapy

G-quadruplex in the TMV Genome Regulates Viral Proliferation and Acts as Antiviral Target of Photodynamic Therapy

In vivo dynamics and regulation of DNA G-quadruplex structures in mammals

Comprehensive Analysis of G-Quadruplexes in African Swine Fever Virus Genome Reveals Potential Antiviral Targets by G-Quadruplex Stabilizers

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