Yavarian Jila, Shafiei Jandaghi Nazanin Zahra, Naseri Maryam, Mokhtari Azad Talat
Virology Department, School of Public Health, Tehran University of Medical Sciences.
Jundishapur J Microbiol. 2014 Mar;7(3):e9089. doi: 10.5812/jjm.9089. Epub 2014 Mar 1.
In the influenza A viruses, neuraminidase (NA), hemagglutinin (HA), PB2, NS1 and M are responsible for the disease pathogenicity. The mechanism of pathogenicity differs among these viruses. Binding of host proteases by the viral NA, sequence of HA in the cleavage and receptor-binding sites, number of oligosaccharide side chains of HA, shortening of NA, and substitutions in PB2, NS1 and M genes, all have been suggested as molecular correlates of pathogenicity of influenza viruses.
The goal of this study was to find the alterations in genes, which might be responsible in the virus pathogenesis.
Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of HA, NA, PB2, NS and M genes were performed.
In the receptor binding site of HA, Ile-226, Pro-227, Ser-228, and Asp-190 were found. Arg was in the cleavage site of all viruses and 11-12 N-linked glycosylation sites were found. In NS1, Asp-92 and Ala-149 were detected and Lys-627 was found in PB2 of all viruses in this study. Val-15, Thr-139 and Ala-218 of M1 and Val-28, Leu-54 and His-57 were found in M2 gene. At residue 146 of NA, there was N-linked glycosylation, and Ile-222 was found in the enzyme active site.
The changes found in these five genes, compared to other studies, suggest that viruses studied in this research had the ability to bind to Neu Acα2,6 Gal linkage and had low pathogenicity. It is important to mention that these changes were at the amino acid level and studies need to be performed on animals to investigate the significance of these findings.
在甲型流感病毒中，神经氨酸酶（NA）、血凝素（HA）、PB2、NS1和M蛋白与疾病致病性有关。这些病毒的致病机制各不相同。病毒NA与宿主蛋白酶的结合、HA在裂解和受体结合位点的序列、HA寡糖侧链的数量、NA的缩短以及PB2、NS1和M基因中的替换，都被认为是流感病毒致病性的分子相关因素。
本研究的目的是找出可能与病毒发病机制有关的基因变化。
进行了HA、NA、PB2、NS和M基因的逆转录聚合酶链反应（RT-PCR）及测序。
在HA的受体结合位点发现了Ile-226、Pro-227、Ser-228和Asp-190。所有病毒的裂解位点均为Arg，且发现了11-12个N-连接糖基化位点。在NS1中检测到Asp-92和Ala-149，本研究中所有病毒的PB2中均发现Lys-627。在M1的Val-15、Thr-139和Ala-218以及M2基因的Val-28、Leu-54和His-57位点被发现。在NA的第146位残基处存在N-连接糖基化，且在酶活性位点发现了Ile-222。
与其他研究相比，在这五个基因中发现的变化表明，本研究中所研究的病毒具有与Neu Acα2,6 Gal连接结合的能力且致病性较低。需要提及的是，这些变化是在氨基酸水平上，需要在动物身上进行研究以探讨这些发现的意义。
