MATURATION OF INFLUENZA-A VIRUS HEMAGGLUTININ - ESTIMATES OF THE PH ENCOUNTERED DURING TRANSPORT AND ITS REGULATION BY THE M2 PROTEIN
MATURATION OF INFLUENZA-A VIRUS HEMAGGLUTININ - ESTIMATES OF THE PH ENCOUNTERED DURING TRANSPORT AND ITS REGULATION BY THE M2 PROTEIN
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DOI：
10.1016/0042-6822(92)91187-y
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发表时间：
1992-09-01
期刊：
影响因子：
3.7
通讯作者：
HAY, AJ
中科院分区：
文献类型：
--
作者：
GRAMBAS, S;HAY, AJ
H7甲型流感病毒对金刚烷胺或金刚乙胺引起的M2介导的HA改变的敏感性取决于HA的pH稳定性和运输到特定病毒感染细胞质膜的pH。一系列病毒突变体的pH稳定性与药物敏感性和在无药物情况下感染细胞表面表达的低pH HA比例呈负相关。因此，运输过程中遇到的最低pH是根据其天然构象中HA的比例和其pH稳定性曲线来估计的。与CEF相比，MDCK细胞对药物的敏感性较低，HA的成熟程度较高，反映了前者适当隔室内较高的pH。感染两个密切相关的病毒株Rostock或Weybridge导致的表观pH差异，例如在CEF中分别约为6.0和5.4，可通过金刚乙胺处理(CEF中约为5.2)来消除，并归因于它们各自M2蛋白的固有特性。Rostock M2的较大活性与HA的较低pH稳定性有关，据估计，该M2能够使泡囊pH提高多达0.8个pH单位。这强调了两种病毒蛋白特性之间的本质联系，以及M2在调节运输途径的pH以保护血凝素糖蛋白结构完整性方面的微妙作用。
The susceptibility of H7 influenza A viruses to the M2-mediated alteration in HA resulting from treatment with amantadine or rimantadine depends both on the pH stability of HA and the pH encountered during transport to the plasma membrane of the particular virus-infected cell. pH stabilities of a range of virus mutant HAs exhibited an inverse correlation with drug sensitivity and the proportion of low-pH HA expressed on the surface of infected cells in the absence of drug. The lowest pH encountered during transport was thus estimated from the proportion of HA expressed in its native conformation and its pH stability profile. Lower drug sensitivity and improved HA maturation in MDCK cells compared to that in CEF reflect the higher pH within the appropriate compartment of the former. Differences in apparent pH resulting from infection with two closely related virus strains, Rostock or Weybridge, e.g., approximately 6.0 and 5.4, respectively, in CEF, were abrogated by rimantadine treatment (pH approximately 5.2 in CEF) and were attributable to intrinsic properties of their respective M2 proteins. The greater activity of the Rostock M2, which was estimated to be capable of increasing vesicular pH by as much as 0.8 pH units, correlates with the lower pH stability of the HA. This emphasizes the essential relationship between the characteristics of the two virus proteins as well as the subtle role of M2 in regulating the pH of the transport pathway to protect the structural integrity of the hemagglutinin glycoprotein.