Byrd-Leotis Lauren, Cummings Richard D, Steinhauer David A
Department Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30307, USA.
Department of Surgery, Harvard Medical School Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Int J Mol Sci. 2017 Jul 17;18(7):1541. doi: 10.3390/ijms18071541.
The hemagglutinin (HA) and neuraminidase (NA) glycoproteins of influenza A virus are responsible for the surface interactions of the virion with the host. Entry of the virus is mediated by functions of the HA: binding to cellular receptors and facilitating fusion of the virion membrane with the endosomal membrane. The HA structure contains receptor binding sites in the globular membrane distal head domains of the trimer, and the fusion machinery resides in the stem region. These sites have specific characteristics associated with subtype and host, and the differences often define species barriers. For example, avian viruses preferentially recognize α2,3-Sialic acid terminating glycans as receptors and mammalian viruses recognize α2,6-Sialic acid. The neuraminidase, or the receptor-destroying protein, cleaves the sialic acid from cellular membrane constituents and viral glycoproteins allowing for egress of nascent virions. A functional balance of activity has been demonstrated between the two glycoproteins, resulting in an optimum level of HA affinity and NA enzymatic cleavage to allow for productive infection. As more is understood about both HA and NA, the relevance for functional balance between HA and NA continues to expand, with potential implications for interspecies transmission, host adaptation, and pathogenicity.
甲型流感病毒的血凝素（HA）和神经氨酸酶（NA）糖蛋白负责病毒粒子与宿主之间的表面相互作用。病毒的进入由HA的功能介导：与细胞受体结合并促进病毒粒子膜与内体膜融合。HA结构在三聚体的球状膜远端头部结构域中包含受体结合位点，融合机制位于茎区。这些位点具有与亚型和宿主相关的特定特征，这些差异通常决定了物种屏障。例如，禽流感病毒优先识别以α2,3-唾液酸结尾的聚糖作为受体，而哺乳动物病毒识别α2,6-唾液酸。神经氨酸酶，即受体破坏蛋白，从细胞膜成分和病毒糖蛋白上切割唾液酸，使新生病毒粒子得以释放。已证明这两种糖蛋白之间存在功能活性平衡，从而导致HA亲和力和NA酶切达到最佳水平，以实现有效的感染。随着对HA和NA的了解越来越多，HA和NA之间功能平衡的相关性不断扩大，对种间传播、宿主适应性和致病性可能产生影响。
