Amino acid determinants conferring stable sialidase activity at low pH for H5N1 influenza A virus neuraminidase.

Amino acid determinants conferring stable sialidase activity at low pH for H5N1 influenza A virus neuraminidase.
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DOI:
10.1016/j.fob.2012.08.007
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发表时间:
2012
期刊:
影响因子:
2.6
通讯作者:
Kawaoka Y
Kawaoka Y
中科院分区:
生物学4区
文献类型:
--
作者:
Takahashi T;Nidom CA;Quynh Le MT;Suzuki T;Kawaoka Y

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禽流感A病毒(IAV)和人类1918年、1957年和1968年大流行IAV都具有在低pH唾液酸酶活性下稳定的神经氨酸酶(NA),但大多数人类流行IAV不具有。我们研究了H5N1高致病性禽IAV(HPAI)NAs的pH稳定性,并确定了负责在低pH下赋予稳定性的氨基酸。我们发现,与其他禽流感病毒不同,自2003年以来分离的大多数H5N1 IAV具有在低pH下不稳定的NAs,类似于人类流行性IAV。因此,这些H5N1病毒已经是人类病毒样的,因此经常感染人类。A型禽流感病毒(IAV)的所有神经氨酸酶(NAs)在低pH下都是稳定的。1968年大流行IAV也具有在低pH下稳定的NA。1968年大流行IAV具有在低pH下不稳定的NA。1969年以来分离的大多数H5N1 IAV的NA在低pH下不稳定。1969年H5N1 IAV NA在低pH下的不稳定性可能解释了频繁的人类感染
Avian influenza A viruses (IAVs) and human 1918, 1957, and 1968 pandemic IAVs all have neuraminidases (NAs) that are stable at low pH sialidase activity, yet most human epidemic IAVs do not. We examined the pH stability of H5N1 highly pathogenic avian IAV (HPAI) NAs and identified amino acids responsible for conferring stability at low pH. We found that, unlike other avian viruses, most H5N1 IAVs isolated since 2003 had NAs that were unstable at low pH, similar to human epidemic IAVs. These H5N1 viruses are thus already human virus-like and, therefore, have the frequent infections of humans. ▸ All neuraminidases (NAs) of avian influenza A viruses (IAVs) are stable at low pH. ▸ Human 1918, 1957, and 1968 pandemic IAVs also have NAs that are stable at low pH. ▸ Most human epidemic IAVs have NAs that are unstable at low pH. ▸ The NAs of most H5N1 IAVs isolated since 2003 are unstable at low pH. ▸ Instability of H5N1 IAV NAs at low pH might explain frequent human infections.
导致 H5N1 甲型流感病毒毒力和发病机制增加的特殊神经氨酸酶茎基序
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