Avian influenza A viruses exhibit plasticity in sialylglycoconjugate receptor usage in human lung cells.

Avian influenza A viruses exhibit plasticity in sialylglycoconjugate receptor usage in human lung cells.
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DOI:
10.1128/jvi.00906-23
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发表时间:
2023-11-30
影响因子:
5.4
通讯作者:
--
中科院分区:
医学2区
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--
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甲型流感病毒(IAV)利用含有细胞表面糖缀合物的唾液酸(Sia)感染宿主细胞,来自不同宿主物种的IAV毒株在糖缀合物末端表现出结构不同的Sia偏好。不同类型的细胞表面糖缀合物(n -聚糖、o -聚糖、糖脂)在结构和碳水化合物组成上都表现出显著的多样性。为了确定促进IAV感染的唾液基糖缀合物的类型,我们利用CRISPR/Cas9技术,通过靶向人肺上皮细胞系中聚糖生物合成所必需的糖基转移酶,截断了三种主要类型的糖缀合物,无论是单独的还是组合的。我们的研究表明,人和禽流感病毒株对特定类型的糖缀合物没有严格的偏好。有趣的是,截断三种主要类型的糖缀合物可显著降低人禽流感病毒株的复制,但不影响禽禽流感病毒株的复制。与人类禽流感病毒株不同,禽流感病毒株能够有效地利用其他不太流行的短糖缀合物,如唾液Tn和唾液T抗原。综上所述,我们的研究表明,与人类禽流感病毒株相比,禽流感病毒株利用更广泛的糖结合物感染宿主细胞。众所周知,甲型流感病毒(IAV)通过与唾液酸结合引发宿主细胞感染,唾液酸是一种存在于各种糖链末端的糖分子,称为糖缀合物。这些糖链的长度、结构和组成各不相同。然而,尚不清楚IAV菌株是否优先结合特定糖缀合物类型的唾液酸来感染宿主细胞。在这里,我们利用CRISPR基因编辑消除了人肺细胞中不同糖缀合物类型上的唾液酸,并评估了人与禽的IAV感染。我们的研究表明,人和禽的IAV毒株都可以利用三种主要的含唾液酸的糖缀合物类型中的任何一种感染人肺细胞,特别是n -聚糖、o -聚糖和糖脂。有趣的是,同时消除人肺细胞中所有三种主要糖缀合物类型的唾液酸可显著降低人IAV感染,但对禽类IAV感染几乎没有影响。这些研究表明,禽流感病毒株有效地利用其他不太流行的糖结合物进行感染,而人类禽流感病毒株依赖于有限的糖结合物类型。禽流感病毒株利用多种糖结合型的显著能力可能使其易于传播到新的宿主物种。
Influenza A viruses (IAV) utilize sialic acid (Sia) containing cell surface glycoconjugates for host cell infection, and IAV strains from different host species show preferences for structurally distinct Sia at the termini of glycoconjugates. Various types of cell surface glycoconjugates (N-glycans, O-glycans, glycolipids) display significant diversity in both structure and carbohydrate composition. To define the types of sialylglycoconjugates that facilitate IAV infection, we utilized the CRISPR/Cas9 technique to truncate the three major types of glycoconjugates, either individually or in combination, by targeting glycosyltransferases essential to glycan biosynthesis in a human lung epithelial cell line. Our studies show that both human and avian IAV strains do not display strict preferences for a specific type of glycoconjugate. Interestingly, truncation of the three major types of glycoconjugates significantly decreased replication of human IAV strains, yet did not impact replication of avian IAV strains. Unlike human IAV strains, avian IAV strains were able to efficiently utilize other less prevalent shorter glycoconjugates such as sialyl Tn and sialyl T antigens. Taken together, our studies demonstrate that avian IAV strains utilize a broader repertoire of glycoconjugates for host cell infection as compared to human IAV strains. It is well known that influenza A viruses (IAV) initiate host cell infection by binding to sialic acid, a sugar molecule present at the ends of various sugar chains called glycoconjugates. These sugar chains can vary in chain length, structure, and composition. However, it remains unknown if IAV strains preferentially bind to sialic acid on specific glycoconjugate type(s) for host cell infection. Here, we utilized CRISPR gene editing to abolish sialic acid on different glycoconjugate types in human lung cells, and evaluated human versus avian IAV infections. Our studies show that both human and avian IAV strains can infect human lung cells by utilizing any of the three major sialic acid-containing glycoconjugate types, specifically N-glycans, O-glycans, and glycolipids. Interestingly, simultaneous elimination of sialic acid on all three major glycoconjugate types in human lung cells dramatically decreased human IAV infection, yet had little effect on avian IAV infection. These studies show that avian IAV strains effectively utilize other less prevalent glycoconjugates for infection, whereas human IAV strains rely on a limited repertoire of glycoconjugate types. The remarkable ability of avian IAV strains to utilize diverse glycoconjugate types may allow for easy transmission into new host species.
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发表时间: 2017-01-11
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发表时间: 2021-02-08
期刊: Viruses
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