Antisense oligonucleotides targeting the RNA binding region of the NP gene inhibit replication of highly pathogenic avian influenza virus H5N1

Zhang, Tao; Wang, Tiecheng; Zhao, Pingsen; Meng, Lingjun; Gao, Yuwei; Wang, Cuiling; Qin, Chuan; Wang, Chengyu; Xia, Xianzhu

doi:10.1016/j.intimp.2011.08.019

Cited by 24 publications

(29 citation statements)

References 28 publications

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“…It should be noted that the use of the proposed TiO 2 ·PL–DNA nanocomposites leads to the more efficient inhibition of the IAV replication as compared to the data of other researchers who used NA-based agents against IAV segment 5 [8–16]. …”

Section: Resultsmentioning

confidence: 86%

“…In order to inhibit the different subtypes of viruses, these regions should have conservative nucleotide sequences and be accessible for the interaction with complementary oligonucleotides. As many other researchers have [8–16], we have chosen segment 5 (encoding nucleoprotein (NP)) of IAV genome as a target to affect the virus replication. To find the most conservative regions of segment 5, we analyzed nucleotide sequences of various subtypes of IAV available in the NCBI Influenza Virus Resource database (http://www.ncbi.nlm.nih.gov).…”

Section: Resultsmentioning

confidence: 99%

“…The coding region close to the stop codon was often used as the target for the action of siRNA [9,12,15–16]. The other regions of the NP gene were also studied as targets [8,11–12 21]. It can be concluded from these literature data that the most susceptible regions for the action of NA-based drugs are the first two regions mentioned above.…”

Section: Resultsmentioning

confidence: 99%

“…The NP plays a key role in the migration of the viral RNAs to cell nuclei of infected cells and in the following replication and assembly of the virus [7]. Therefore, many researchers believe that segment 5, which encodes this protein, is an ideal target to block the virus reproduction by antiviral compounds [8–10]. …”

Section: Introductionmentioning

confidence: 99%

“…Different regions of segment 5 have been studied for their sensitivity to the action of NA-based drugs of various nature [8–16]. However, there is still no unified concept for the most vulnerable regions of this segment.…”

Section: Introductionmentioning

confidence: 99%

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High antiviral effect of TiO₂·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

Левина¹,

Репкова²,

Bessudnova³

et al. 2016

Beilstein J. Nanotechnol.

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Summary Background: The development of new antiviral drugs based on nucleic acids is under scrutiny. An important problem in this aspect is to find the most vulnerable conservative regions in the viral genome as targets for the action of these agents. Another challenge is the development of an efficient system for their delivery into cells. To solve this problem, we proposed a TiO2·PL–DNA nanocomposite consisting of titanium dioxide nanoparticles and polylysine (PL)-containing oligonucleotides. Results: The TiO2·PL–DNA nanocomposites bearing the DNA fragments targeted to different conservative regions of (−)RNA and (+)RNA of segment 5 of influenza A virus (IAV) were studied for their antiviral activity in MDCK cells infected with the H1N1, H5N1, and H3N2 virus subtypes. Within the negative strand of each of the studied strains, the efficiency of DNA fragments increased in the direction of its 3’-end. Thus, the DNA fragment aimed at the 3’-noncoding region of (−)RNA was the most efficient and inhibited the reproduction of different IAV subtypes by 3–4 orders of magnitude. Although to a lesser extent, the DNA fragments targeted at the AUG region of (+)RNA and the corresponding region of (−)RNA were also active. For all studied viral subtypes, the nanocomposites bearing the DNA fragments targeted to (−)RNA appeared to be more efficient than those containing fragments aimed at the corresponding (+)RNA regions. Conclusion: The proposed TiO2·PL–DNA nanocomposites can be successfully used for highly efficient and site-specific inhibition of influenza A virus of different subtypes. Some patterns of localization of the most vulnerable regions in IAV segment 5 for the action of DNA-based drugs were found. The (−)RNA strand of IAV segment 5 appeared to be more sensitive as compared to (+)RNA.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High antiviral effect of TiO₂·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

Левина¹,

Репкова²,

Bessudnova³

et al. 2016

Beilstein J. Nanotechnol.

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Mouse adaptation of the H9N2 avian influenza virus causes the downregulation of genes related to innate immune responses and ubiquitin-mediated proteolysis in mice

Guo

Gao

Liu

et al. 2020

Med Microbiol Immunol

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H9N2 avian influenza viruses sporadically infect humans worldwide. These viruses have also contributed internal genes to H5N1, H5N6, H7N9, and H10N8 viruses, which have been isolated from humans with infections and are a substantial public health threat. To investigate the potential pathogenic mechanism of the H9N2 virus, we performed serial lung-to-lung passage of an avirulent H9N2 avian influenza virus (A/Chicken/Shandong/416/2016 [SD/416]) in mice to increase the pathogenicity of this virus. We generated a mouse-adapted (MA) virus that exhibited increased viral titers in the lungs, caused severe lung damage in mice, and induced body weight loss in mice; however, the avirulent parental virus did not cause any clinical symptoms in infected mice. Global gene expression analysis was performed and indicated that the transcriptional responses of these viruses were distinct. The lungs of mice infected with the MA virus exhibited the downregulation of genes related to innate immunity and ubiquitin-mediated proteolysis, which was not seen in infections with the avirulent parental virus. These data indicated that the MA virus might evade immune surveillance and changed its replication capacity to increase the viral replication level and pathogenicity. Our study demonstrates that host factors play an important role in the adaptive evolution of influenza virus in new hosts.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Knockdown of different influenza A virus subtypes in cell culture by a single antisense oligodeoxyribonucleotide

Левина

Репкова

Мазуркова

et al. 2015

International Journal of Antimicrobial Agents

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Antisense oligonucleotides targeting the RNA binding region of the NP gene inhibit replication of highly pathogenic avian influenza virus H5N1

Cited by 24 publications

References 28 publications

High antiviral effect of TiO₂·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

High antiviral effect of TiO₂·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

Mouse adaptation of the H9N2 avian influenza virus causes the downregulation of genes related to innate immune responses and ubiquitin-mediated proteolysis in mice

Knockdown of different influenza A virus subtypes in cell culture by a single antisense oligodeoxyribonucleotide

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Antisense oligonucleotides targeting the RNA binding region of the NP gene inhibit replication of highly pathogenic avian influenza virus H5N1

Cited by 24 publications

References 28 publications

High antiviral effect of TiO2·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

High antiviral effect of TiO2·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

Mouse adaptation of the H9N2 avian influenza virus causes the downregulation of genes related to innate immune responses and ubiquitin-mediated proteolysis in mice

Knockdown of different influenza A virus subtypes in cell culture by a single antisense oligodeoxyribonucleotide

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High antiviral effect of TiO₂·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture

High antiviral effect of TiO₂·PL–DNA nanocomposites targeted to conservative regions of (−)RNA and (+)RNA of influenza A virus in cell culture