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给予 E2 和 NS1 siRNA 可抑制体外的基孔肯雅病毒复制，并保护感染该病毒的小鼠。

Administration of E2 and NS1 siRNAs inhibit chikungunya virus replication in vitro and protects mice infected with the virus.

机构信息

National Institute of Virology, Microbial Containment Complex, Sus Road, Pashan, Pune, India.

出版信息

PLoS Negl Trop Dis. 2013 Sep 5;7(9):e2405. doi: 10.1371/journal.pntd.0002405. eCollection 2013.

DOI:10.1371/journal.pntd.0002405
PMID:24040429
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3764232/
Abstract

BACKGROUND

Chikungunya virus (CHIKV) has reemerged as a life threatening pathogen and caused large epidemics in several countries. So far, no licensed vaccine or effective antivirals are available and the treatment remains symptomatic. In this context, development of effective and safe prophylactics and therapeutics assumes priority.

METHODS

We evaluated the efficacy of the siRNAs against ns1 and E2 genes of CHIKV both in vitro and in vivo. Four siRNAs each, targeting the E2 (Chik-1 to Chik-4) and ns1 (Chik-5 to Chik-8) genes were designed and evaluated for efficiency in inhibiting CHIKV growth in vitro and in vivo. Chik-1 and Chik-5 siRNAs were effective in controlling CHIKV replication in vitro as assessed by real time PCR, IFA and plaque assay.

CONCLUSIONS

CHIKV replication was completely inhibited in the virus-infected mice when administered 72 hours post infection. The combination of Chik-1 and Chik-5 siRNAs exhibited additive effect leading to early and complete inhibition of virus replication. These findings suggest that RNAi capable of inhibiting CHIKV growth might constitute a new therapeutic strategy for controlling CHIKV infection and transmission.

摘要

背景

基孔肯雅病毒（CHIKV）再次出现，成为一种威胁生命的病原体，并在多个国家引发了大规模疫情。迄今为止，尚无许可疫苗或有效的抗病毒药物可用，治疗仍然是对症治疗。在这种情况下，开发有效和安全的预防和治疗方法成为当务之急。

方法

我们评估了针对 CHIKV 的 ns1 和 E2 基因的 siRNAs 的体外和体内疗效。设计了针对 E2（Chik-1 至 Chik-4）和 ns1（Chik-5 至 Chik-8）基因的每种 4 个 siRNAs，以评估其在体外和体内抑制 CHIKV 生长的效率。Chik-1 和 Chik-5 siRNAs 通过实时 PCR、IFA 和噬斑测定在体外有效控制 CHIKV 复制。

结论

当在感染后 72 小时给予时，感染病毒的小鼠中的 CHIKV 复制完全受到抑制。Chik-1 和 Chik-5 siRNAs 的组合表现出相加作用，导致病毒复制的早期和完全抑制。这些发现表明，能够抑制 CHIKV 生长的 RNAi 可能构成控制 CHIKV 感染和传播的新治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/09e35a2252bf/pntd.0002405.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/8984d2841754/pntd.0002405.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/3ebf6c83ae3f/pntd.0002405.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/0edc963de865/pntd.0002405.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/7d3e81d7ee2b/pntd.0002405.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/c8550cd80a6e/pntd.0002405.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/56001cffd747/pntd.0002405.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/6b652effeb80/pntd.0002405.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/5ed1c83dbfd9/pntd.0002405.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/fb5d695ebc22/pntd.0002405.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/09e35a2252bf/pntd.0002405.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/8984d2841754/pntd.0002405.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/3ebf6c83ae3f/pntd.0002405.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/0edc963de865/pntd.0002405.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/7d3e81d7ee2b/pntd.0002405.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/c8550cd80a6e/pntd.0002405.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/56001cffd747/pntd.0002405.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/6b652effeb80/pntd.0002405.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/5ed1c83dbfd9/pntd.0002405.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/fb5d695ebc22/pntd.0002405.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/991c/3764232/09e35a2252bf/pntd.0002405.g010.jpg

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