Dataset Information

Inhibition of highly pathogenic avian influenza (HPAI) virus by a peptide derived from vFLIP through its direct destabilization of viruses.

ABSTRACT: The antiviral activities of synthesized K?2-helix peptide, which was derived from the viral FLICE-like inhibitor protein (vFLIP) of Kaposi's sarcoma-associated herpesvirus (KSHV), against influenza A virus (IAV) were investigated in vitro and in vivo, and mechanisms of action were suggested. In addition to the robust autophagy activity of the K?2-helix peptide, the present study showed that treatment with the K?2 peptide fused with the TAT peptide significantly inhibited IAV replication and transmission. Moreover, TAT-K?2 peptide protected the mice, that were challenged with lethal doses of highly pathogenic influenza A H5N1 or H1N1 viruses. Mechanistically, we found that TAT-K?2 peptide destabilized the viral membranes, depending on their lipid composition of the viral envelop. In addition to IAV, the K?2 peptide inhibited infections with enveloped viruses, such as Vesicular Stomatitis Virus (VSV) and Respiratory Syncytial Virus (RSV), without cytotoxicity. These results suggest that TAT-K?2 peptide is a potential antiviral agent for controlling emerging or re-emerging enveloped viruses, particularly diverse subtypes of IAVs.

SUBMITTER: Moon HJ

PROVIDER: S-EPMC5501782 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Inhibition of highly pathogenic avian influenza (HPAI) virus by a peptide derived from vFLIP through its direct destabilization of viruses.

Moon Ho-Jin HJ Nikapitiya Chamilani C Lee Hyun-Cheol HC Park Min-Eun ME Kim Jae-Hoon JH Kim Tae-Hwan TH Yoon Ji-Eun JE Cho Won-Kyung WK Ma Jin Yeul JY Kim Chul-Joong CJ Jung Jae U JU Lee Jong-Soo JS

Scientific reports 20170707 1

The antiviral activities of synthesized Kα2-helix peptide, which was derived from the viral FLICE-like inhibitor protein (vFLIP) of Kaposi's sarcoma-associated herpesvirus (KSHV), against influenza A virus (IAV) were investigated in vitro and in vivo, and mechanisms of action were suggested. In addition to the robust autophagy activity of the Kα2-helix peptide, the present study showed that treatment with the Kα2 peptide fused with the TAT peptide significantly inhibited IAV replication and tran ...[more]

PMID: 28687749

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Project description:Over the past years, many different control measures have been implemented to prevent HPAI infection. The national plan with numerous measures lead to problems in terms of prioritization and budget allocation. Our study objectives are to (i) establish an inventory of measures on HPAI control in Indonesia since the first actions were taken in 2004, (ii) evaluate preferences for different HPAI control measures applied in the West Java province at the district level during 2013-2017, and (iii) establish a basis for further qualitative and quantitative research to improve control for an endemic HPAI in Indonesia. This research was carried out according to the following five steps (i) development of an HPAI management framework for an endemic state, (ii) inventorization of measures directed at HPAI and description of the development of HPAI in Indonesia, (iii) development of a questionnaire for the experts involved, (iv) systematic evaluation of preferences for short- and long-term HPAI strategies and measures applied in the West Java Province based on expert opinion, and (v) data analysis. The study systematically evaluated in total 27 measures. The results of this study show that the animal disease management framework is helpful as a systematic structure to distinguish and evaluate strategies and measures. In our framework, we defined the following strategies: prevention, monitoring, control, mitigation, eradication, and human protection. The findings of our research show that the primary aims of the government were to safeguard humans from HPAI transmission by mitigating HPAI disease in livestock. The measures with the highest priority were preventive vaccination of poultry, biosecurity, and stamping-out infected flocks. This showed that the government predominantly chose a vaccination-based HPAI mitigation strategy. However, the chosen strategy has a low implementation feasibility. A collaboration between the responsible stakeholders farmers may increase the feasibility of the chosen strategy in the future. Furthermore, our findings provide a basis for research into the motivation of farmers to implement different measures as well as into the expected impact of different measures to develop an effective and efficient mitigation approach.

Project description:Highly pathogenic avian influenza (HPAI) H5N1 was first encountered in 1996 in Guangdong province (China) and started spreading throughout Asia and the western Palearctic in 2004-2006. Compared to several other countries where the HPAI H5N1 distribution has been studied in some detail, little is known about the environmental correlates of the HPAI H5N1 distribution in China. HPAI H5N1 clinical disease outbreaks, and HPAI virus (HPAIV) H5N1 isolated from active risk-based surveillance sampling of domestic poultry (referred to as HPAIV H5N1 surveillance positives in this manuscript) were modeled separately using seven risk variables: chicken, domestic waterfowl population density, proportion of land covered by rice or surface water, cropping intensity, elevation, and human population density. We used bootstrapped logistic regression and boosted regression trees (BRT) with cross-validation to identify the weight of each variable, to assess the predictive power of the models, and to map the distribution of HPAI H5N1 risk. HPAI H5N1 clinical disease outbreak occurrence in domestic poultry was mainly associated with chicken density, human population density, and elevation. In contrast, HPAIV H5N1 infection identified by risk-based surveillance was associated with domestic waterfowl density, human population density, and the proportion of land covered by surface water. Both models had a high explanatory power (mean AUC ranging from 0.864 to 0.967). The map of HPAIV H5N1 risk distribution based on active surveillance data emphasized areas south of the Yangtze River, while the distribution of reported outbreak risk extended further North, where the density of poultry and humans is higher. We quantified the statistical association between HPAI H5N1 outbreak, HPAIV distribution and post-vaccination levels of seropositivity (percentage of effective post-vaccination seroconversion in vaccinated birds) and found that provinces with either outbreaks or HPAIV H5N1 surveillance positives in 2007-2009 appeared to have had lower antibody response to vaccination. The distribution of HPAI H5N1 risk in China appears more limited geographically than previously assessed, offering prospects for better targeted surveillance and control interventions.

Dataset Information

Inhibition of highly pathogenic avian influenza (HPAI) virus by a peptide derived from vFLIP through its direct destabilization of viruses.

Publications

Inhibition of highly pathogenic avian influenza (HPAI) virus by a peptide derived from vFLIP through its direct destabilization of viruses.

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