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

Abstract

Whether chicken Mx inhibits influenza virus replication is an important

Mx Is Dispensable for Interferon-Mediated Resistance of Chicken Cells against Influenza A Virus

“…Neither of these proteins was able to reduce FLUAV replication in our hands, confirming earlier observations from other experimental setups by us and others (5,7). In contrast, the expression of mouse Mx1 and human MxA resulted in a strong protective effect against lowly and highly pathogenic FLUAV from both human and avian origin.…”

“…Later, Ko and coworkers reported that a singlenucleotide polymorphism at amino acid 631 is crucial for virus protection by chicken Mx (20). More recent reports from several laboratories are conflicting, some assigning and some not assigning antiviral activity to the chicken Mx protein (5,6,9,19,20,39,43). Thus, the question of whether Mx contributes to influenza virus resistance in the chicken has remained unanswered.…”

“…However, FLUAV infection experiments with chickens of defined Mx-631 genotypes failed to show a correlation between susceptibility and Mx isoform (39). Furthermore, using chicken embryo fibroblasts (CEF) from different chicken lines with Mx-631Ser or Mx-631Asn as well as human HEK293T cells expressing the Mx-631Asn isoform, Benfield and coworkers were not able to confirm the proposed antiviral activity of the Mx-631Asn variant toward different FLUAV strains (5).…”

PCR-RFLP genotyping protocol for chicken Mx gene G/A polymorphism associated with the S631N mutation

“…However, no association was found between the Mx genotype for the G/A polymorphism affecting amino acid position 631 and the survival of chicken experimentally infected in vivo with a highly pathogenic H7N1 avian influenza virus (Sironi et al, 2008). Similar results were obtained by Benfield et al (2008) in their study showing that the Asn631 allele of chicken Mx is unable to inhibit in vitro replication of 5 influenza strains.…”

The Viral Nucleoprotein Determines Mx Sensitivity of Influenza A Viruses

“…Mx genes are also present in avian species, and some antiviral activity for chicken Mx linked to a serine-to-asparagine polymorphism at position 631 has been described (15). However, recent studies could not detect any antiviral effect of chicken Mx proteins against different strains of influenza A viruses (3,27). In any case, it is conceivable that newly emerging influenza A viruses acquire adaptive mutations in the mammalian host which allow them to escape Mx restriction.…”