TY - JOUR
T1 - Amino acid substitution at position 44 of matrix protein 2 of an avirulent H5 avian influenza virus is crucial for acquiring the highly pathogenic phenotype in chickens
AU - Fujimoto, Yoshikazu
AU - Ito, Hiroshi
AU - Tomita, Megumi
AU - Ono, Etsuro
AU - Usui, Tatsufumi
AU - Ito, Toshihiro
PY - 2015/8/13
Y1 - 2015/8/13
N2 - The pathogenicity of highly pathogenic avian influenza (HPAI) viruses is dependent on multiple factors, but the sequence at the HA cleavage site plays the most important role. To better understand the mechanism of virulence of HPAI virus, an avirulent H5 avian influenza virus, A/teal/Tottori/150/02 (H5N3, teal/150), was passaged in respiratory organs of chickens to generate a virus with a highly pathogenic phenotype. After 12 consecutive passages, the virus (strain 12a) became highly pathogenic, with a 100 % mortality rate in chickens. Sequence analysis of the highly pathogenic variant revealed an amino acid change from aspartic acid (Asp) to asparagine (Asn) at position 44 of matrix protein 2 (M2). To investigate the role of M2 in the pathogenicity of HPAI virus, we generated reassortant viruses possessing a polybasic HA cleavage site and either Asp or Asn at position 44 of M2 using the highly pathogenic strain 12a and the avirulent strain 7a, which has Asp at position 44 of M2 derived from isolate teal/150, and we compared their pathogenicity in chickens. Experimental infections demonstrated that the pathogenicity of viruses possessing Asp in M2 was dramatically decreased, and the mortality rate of inoculated chickens was 0 %, in contrast to viruses with Asn, which showed 70 to 100 % mortality. Our findings indicate that M2 protein of the avirulent H5 avian influenza virus is important for acquiring high virulence and that Asn at position 44 of M2, in addition to the polybasic HA cleavage site, is crucial for high pathogenicity in chickens.
AB - The pathogenicity of highly pathogenic avian influenza (HPAI) viruses is dependent on multiple factors, but the sequence at the HA cleavage site plays the most important role. To better understand the mechanism of virulence of HPAI virus, an avirulent H5 avian influenza virus, A/teal/Tottori/150/02 (H5N3, teal/150), was passaged in respiratory organs of chickens to generate a virus with a highly pathogenic phenotype. After 12 consecutive passages, the virus (strain 12a) became highly pathogenic, with a 100 % mortality rate in chickens. Sequence analysis of the highly pathogenic variant revealed an amino acid change from aspartic acid (Asp) to asparagine (Asn) at position 44 of matrix protein 2 (M2). To investigate the role of M2 in the pathogenicity of HPAI virus, we generated reassortant viruses possessing a polybasic HA cleavage site and either Asp or Asn at position 44 of M2 using the highly pathogenic strain 12a and the avirulent strain 7a, which has Asp at position 44 of M2 derived from isolate teal/150, and we compared their pathogenicity in chickens. Experimental infections demonstrated that the pathogenicity of viruses possessing Asp in M2 was dramatically decreased, and the mortality rate of inoculated chickens was 0 %, in contrast to viruses with Asn, which showed 70 to 100 % mortality. Our findings indicate that M2 protein of the avirulent H5 avian influenza virus is important for acquiring high virulence and that Asn at position 44 of M2, in addition to the polybasic HA cleavage site, is crucial for high pathogenicity in chickens.
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U2 - 10.1007/s00705-015-2470-7
DO - 10.1007/s00705-015-2470-7
M3 - Article
C2 - 26081872
AN - SCOPUS:84938963601
VL - 160
SP - 2063
EP - 2070
JO - Archives of Virology
JF - Archives of Virology
SN - 0304-8608
IS - 8
ER -