Native antiviral specificity of chicken Mx protein depends on amino acid variation at position 631

Abstract

An attempt was made to determine whether amino acid variation at position 631 in the chicken Mx protein definitely influences antiviral specificity, using an artificial mutation technique by which a single amino acid was reciprocally substituted between Ser (AGT) and Asn (AAT) at position 631 of the negative and positive chicken Mx, respectively. Using permanently transfected 3T3 cell lines, the antiviral potential of chicken Mx against vesicular stomatitis virus infection was analysed. The results indicated that the phenotype of antiviral activity depends on the amino acid difference at position 631; that is, the genotype coding Asn at position 631 corresponds to the positive antiviral phenotype, and the genotype coding Ser corresponds to the negative phenotype. The present study has confirmed that the antiviral specificity of chicken Mx protein is determined by an amino acid substitution at the carboxy terminus.

Amelioration of Influenza Virus Pathogenesis in Chickens Attributed to the Enhanced Interferon-Inducing Capacity of a Virus with a Truncated NS1 Gene

“…The Mx system, which was shown to be important in mammalian cells, may be operative in chickens but only infrequently, being restricted to those few birds that have a unique amino acid change in the Mx protein (20). Two other reactants that avian cells produce following virus infection may also contribute to the reduction of virus shedding in AIV-infected chickens: ChIFN-␥ (6, 61), with its capacity to act synergistically with ChIFN-␣ (46), and a secreted dsRNase unique to avian species and coinduced with IFN (34).…”

Asparagine 631 Variants of the Chicken Mx Protein Do Not Inhibit Influenza Virus Replication in Primary Chicken Embryo Fibroblasts or In Vitro Surrogate Assays

“…Constitutive expression of the Mx allele in 3T3 cell lines from a Japanese Shamo (SHK) line of chickens resulted in a 10-to 100-fold reduction in influenza virus titers (14). Certain chicken Mx proteins have also been shown to inhibit replication of vesicular stomatitis virus (VSV) (14), and artificial mutation has demonstrated that the amino acid at position 631 of the chicken Mx protein is a crucial determinant of anti-VSV activity (Asn631 is active and Ser631 is inactive against VSV) (15). SHK Mx also has an Asn residue at position 631, and it has been inferred that this polymorphism is important for anti-influenza activity.…”

Chicken Mx gene polymorphisms in Indian native chicken breeds and White Leghorn by real time multiplex allele specific PCR

“…However, multiplex real time allele specific PCR employed in the current study demonstrated by Ye et al (2010) is simple, robust and effective method for large scale screening. Genotype A at position 2032 corresponds to the asparagine aminoacid at position 631 of Mx protein and has higher antiviral activity than serine aminoacid coded by G at position 2032 (Ko et al, 2004). Thus, genotype A is considered as resistant allele and G as susceptible allele (Seyama et al, 2006;Watanabe, 2007).…”

“…Different alleles of chicken Mx gene have been shown to vary in their antiviral activity against influenza virus in an in vitro infection study and recombinant vesicular stomatitis virus (Bernasconi et al, 1995;Ko et al, 2002). A non-synonymous mutation at position 2032 of chicken Mx gene responsible for variation of aminoacid (Ser to Asn) in protein has been demonstrated to be responsible for negative to positive antiviral activity of Mx protein (Ko et al, 2002(Ko et al, , 2004. Recently this SNP have been demonstrated to confer more resistance in chicken to in vivo experimental infection of highly pathogenic avian influenza virus (HPAIV) (Ewald et al, 2011, Wang et al, 2012, Fulton et al, 2014.…”