| Structural highlights
Function
GLYC_LASSJ Stable signal peptide (SSP) is cleaved but is apparently retained as the third component of the GP complex. The SSP is required for efficient glycoprotein expression, post-translational cleavage of GP1 and GP2, glycoprotein transport to the cell plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion. The GP complex interacts with host glycosylated LAMP1 to mediate efficient infection.[1] Glycoprotein G1 mediates virus attachment to host receptor alpha-dystroglycan DAG1. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis. Glycoprotein G2 is a class I viral fusion protein, that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversable conformational changes induced upon acidification in the endosome (By similarity).
Publication Abstract from PubMed
Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines.
Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies.,Perrett HR, Brouwer PJM, Hurtado J, Newby ML, Liu L, Muller-Krauter H, Muller Aguirre S, Burger JA, Bouhuijs JH, Gibson G, Messmer T, Schieffelin JS, Antanasijevic A, Boons GJ, Strecker T, Crispin M, Sanders RW, Briney B, Ward AB Cell Rep. 2023 May 30;42(5):112524. doi: 10.1016/j.celrep.2023.112524. Epub 2023 , May 18. PMID:37209096[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jae LT, Raaben M, Herbert AS, Kuehne AI, Wirchnianski AS, Soh TK, Stubbs SH, Janssen H, Damme M, Saftig P, Whelan SP, Dye JM, Brummelkamp TR. Virus entry. Lassa virus entry requires a trigger-induced receptor switch. Science. 2014 Jun 27;344(6191):1506-10. doi: 10.1126/science.1252480. PMID:24970085 doi:http://dx.doi.org/10.1126/science.1252480
- ↑ Perrett HR, Brouwer PJM, Hurtado J, Newby ML, Liu L, Müller-Kräuter H, Müller Aguirre S, Burger JA, Bouhuijs JH, Gibson G, Messmer T, Schieffelin JS, Antanasijevic A, Boons GJ, Strecker T, Crispin M, Sanders RW, Briney B, Ward AB. Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies. Cell Rep. 2023 May 30;42(5):112524. PMID:37209096 doi:10.1016/j.celrep.2023.112524
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