virulence of the strain. H5N1 NS1 is characterized by a single amino acid change at position 92. By changing the amino acid from glutamic acid to aspartic acid, researchers were able to annul the effect of the H5N1 NS1. This single amino acid change in the NS1 gene greatly increased the pathogenicity of the H5N1 influenza virus. However, the effect of residue 92 on the function of H5N1 NS1 appears to be questionable as noted by Nature Medicine editors: The above paper originally reported that H5N1 viruses are resistant to interferon in the SJPL cell line. The editors wish to alert our readers about three facts that may affect this conclusion. First, Ngunjiri et al. have recently found that aliquots of the SJPL cell line obtained from the American Type Culture Collection were heavily contaminated with mycoplasma. Although the mycoplasma status of the cells used in the original paper is unknown, it is not possible to rule out that they were contaminated. Second, SJPL cells were originally reported to be of porcine origin, but a recent analysis has indicated that they are of simian origin. Third, Ngunjiri et al. have found H5N1 viruses to be sensitive to interferons in all cell lines tested from multiple species. Pathogenicity The fact that NS1 is involved in the pathogenicity of influenza A viruses makes it a good target to attenuate these viruses. Several studies demonstrated that influenza viruses with partial deletions in NS1 proteins are attenuated and do not cause disease, but induce a protective immune response in different species including mice, pigs, horses, birds and macaques. Although it had been known for more than a decade that influenza viruses with partial deletions in NS1 proteins were attenuated, all but one NS1 truncation variants of influenza A viruses were generated by in vitro mutagenesis. Wang et al. later demonstrated that the naturally truncated variant had propensity to generate new variants when passaged in ovo. Remarkably, the new variants were excellent live-attenuated influenza vaccine candidates. The ability to attenuate influenza viruses by truncation of the NS1 protein presents a novel approach in design and development of the next generation live-attenuated influenza vaccines for both poultry and humans. See also H5N1 genetic structure References External links NCBI Flu Genome Database Proteins Influenza A virus