Despite the potent antiviral activity of Mx1, its utility to protect large animals, such as pigs, fr

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* Corresponding author: Liangxue Lai lai_liangxue@gibh.ac.cn
The electronic version of this article is the complete one and can be found online at: http://www.cellregenerationjournal.com/content/3/1/11 Received: 13 October 2013 Accepted: 25 April 2014 Published: 26 September 2014
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The myxovirus resistance gene (Mx1) has a broad spectrum of antiviral activities. It is therefore an interesting candidate gene to improve disease resistance in farm animals. In this study, we report the use of somatic cell nuclear transfer (SCNT) purton vets to produce transgenic pigs over-expressing the Mx1 gene. These transgenic pigs express approximately 15 25 times more Mx1 mRNA than non-transgenic pigs, and the protein level of Mx1 was also markedly enhanced. We challenged fibroblast cells isolated from the ear skin of transgenic and control pigs with influenza A virus and classical swine fever virus (CFSV). Indirect immunofluorescence assay (IFA) revealed a profound decrease of influenza A proliferation in Mx1 transgenic cells. Growth kinetics showed an approximately 10-fold reduction of viral copies in the transgenic cells compared to non-transgenic controls. Additionally, we found that the Mx1 transgenic cells were more resistant to CSFV infection in comparison to non-transgenic cells. These results demonstrate that the Mx1 transgene can protect against viral infection purton vets in cells of transgenic pigs and indicate that the Mx1 transgene can be harnessed to develop disease-resistant pigs. Keywords: Antiviral breeding; Innate purton vets resistance; Somatic cell nuclear transfer Introduction
Type I interferons (IFNs) are important mediators of the innate immune responses and are crucial for limiting the early replication and spread of viruses [ 1 ]. An important downstream effector of type I IFNs is the myxovirus resistance gene (Mx1 in mice and pigs, MxA in humans). The expression of Mx1 is strongly induced by IFN-α/β,double-stranded RNA or viral infections purton vets [ 2 , 3 ]. The Mx1 protein can protect numerous purton vets hosts by preventing the growth of a wide variety of viruses both in vitro and in vivo including orthomyxoviruses [ 4 - 6 ], bunyaviruses [ 7 , 8 ], rhabdoviruses [ 9 ], paramyxoviruses [ 10 ] and hantaviruses [ 11 , 12 ]. Several studies showed that stably transfected cells constitutively expressing chicken, mouse, purton vets pig or human Mx1/MxA proteins effectively inhibited the replication of several RNA viruses [ 13 - 19 ]. Specifically, transgenic mice expressing mouse Mx1 or human MxA also showed enhanced resistance purton vets to the influenza A virus as well as to several other viruses [ 20 , 21 ]. Collectively, these studies showed that the resistance of transgenic mice to viral infection was not due to broad immunological activation in response to the virus. Rather, Mx1/MxA proteins exert their antiviral effects by directly inhibiting replication of the viral genome.
Despite the potent antiviral activity of Mx1, its utility to protect large animals, such as pigs, from viral infection has not yet been explored. Pigs are susceptible to swine, human and avian influenza viruses. As alternate hosts, pigs are believed to be mixing vessels by enabling the genetic rearrangement of influenza purton vets viruses and thereby purton vets amplify their genetic variation. As a consequence, the probability of influenza pandemics threatening humans is increased [ 22 ]. A recent report revealed that the circulating pandemic H1N1/2009 influenza A virus originated in pigs and contained genetic contributions of human, avian and swine influenza viruses [ 23 ]. Therefore, influenza resistant pigs would not only benefit the livestock industry but also global public health by eliminating a critical host so that new variants of pandemic influenza strains can no longer emerge. Mx1 is an interesting candidate gene to engineer pigs with enhanced viral resistance. Besides influenza, Mx1 is also expected to lead to resistance for other severe swine infectious viruses such as CSFV. As the use of swine vaccines to prevent these diseases is very costly, the production of genetically modified pigs that possess congenital resistance to viral infect