| Structural highlights
Function
A7Y8I1_9INFA Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization either through clathrin-dependent endocytosis or through clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.[HAMAP-Rule:MF_04072][SAAS:SAAS01039073] Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.[RuleBase:RU003324]
Publication Abstract from PubMed
Current influenza vaccines predominantly induce immunity to the hypervariable hemagglutinin (HA) head, requiring frequent vaccine reformulation. Conversely, the immunosubdominant yet conserved HA stem harbors a supersite that is targeted by broadly neutralizing antibodies (bnAbs), representing a prime target for universal vaccines. Here, we showed that the co-immunization of two HA stem immunogens derived from group 1 and 2 influenza A viruses elicits cross-group protective immunity and neutralizing antibody responses in mice, ferrets, and nonhuman primates (NHPs). Immunized mice were protected from multiple group 1 and 2 viruses, and all animal models showed broad serum-neutralizing activity. A bnAb isolated from an immunized NHP broadly neutralized and protected against diverse viruses, including H5N1 and H7N9. Genetic and structural analyses revealed strong homology between macaque and human bnAbs, illustrating common biophysical constraints for acquiring cross-group specificity. Vaccine elicitation of stem-directed cross-group-protective immunity represents a step toward the development of broadly protective influenza vaccines.
Co-immunization with hemagglutinin stem immunogens elicits cross-group neutralizing antibodies and broad protection against influenza A viruses.,Moin SM, Boyington JC, Boyoglu-Barnum S, Gillespie RA, Cerutti G, Cheung CS, Cagigi A, Gallagher JR, Brand J, Prabhakaran M, Tsybovsky Y, Stephens T, Fisher BE, Creanga A, Ataca S, Rawi R, Corbett KS, Crank MC, Karlsson Hedestam GB, Gorman J, McDermott AB, Harris AK, Zhou T, Kwong PD, Shapiro L, Mascola JR, Graham BS, Kanekiyo M Immunity. 2022 Dec 13;55(12):2405-2418.e7. doi: 10.1016/j.immuni.2022.10.015. , Epub 2022 Nov 9. PMID:36356572[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Moin SM, Boyington JC, Boyoglu-Barnum S, Gillespie RA, Cerutti G, Cheung CS, Cagigi A, Gallagher JR, Brand J, Prabhakaran M, Tsybovsky Y, Stephens T, Fisher BE, Creanga A, Ataca S, Rawi R, Corbett KS, Crank MC, Karlsson Hedestam GB, Gorman J, McDermott AB, Harris AK, Zhou T, Kwong PD, Shapiro L, Mascola JR, Graham BS, Kanekiyo M. Co-immunization with hemagglutinin stem immunogens elicits cross-group neutralizing antibodies and broad protection against influenza A viruses. Immunity. 2022 Dec 13;55(12):2405-2418.e7. doi: 10.1016/j.immuni.2022.10.015. , Epub 2022 Nov 9. PMID:36356572 doi:http://dx.doi.org/10.1016/j.immuni.2022.10.015
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