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Structure paper

タイトル	Crimean-Congo hemorrhagic fever survivors elicit protective non-neutralizing antibodies that target 11 overlapping regions on glycoprotein GP38.
ジャーナル・号・ページ	Cell Rep, Vol. 43, Issue 7, Page 114502, Year 2024
掲載日	2024年7月12日
著者	Olivia S Shin / Stephanie R Monticelli / Christy K Hjorth / Vladlena Hornet / Michael Doyle / Dafna Abelson / Ana I Kuehne / Albert Wang / Russell R Bakken / Akaash K Mishra / Marissa Middlecamp / Elizabeth Champney / Lauran Stuart / Daniel P Maurer / Jiannan Li / Jacob Berrigan / Jennifer Barajas / Stephen Balinandi / Julius J Lutwama / Leslie Lobel / Larry Zeitlin / Laura M Walker / John M Dye / Kartik Chandran / Andrew S Herbert / Noel T Pauli / Jason S McLellan /
PubMed 要旨	Crimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, exclusive to Nairoviridae, is a target of ...Crimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, exclusive to Nairoviridae, is a target of protective antibodies and is a key antigen in preclinical vaccine candidates. Here, we isolate 188 GP38-specific antibodies from human survivors of infection. Competition experiments show that these antibodies bind across 5 distinct antigenic sites, encompassing 11 overlapping regions. Additionally, we show structures of GP38 bound with 9 of these antibodies targeting different antigenic sites. Although these GP38-specific antibodies are non-neutralizing, several display protective efficacy equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and may inform the development of broadly effective CCHFV antibody therapeutics.
リンク	Cell Rep / PubMed:39002130
手法	EM (単粒子) / X線回折
解像度	1.8 - 5.6 Å
構造データ	EMDB-43551: CCHFV GP38 bound with ADI-46143 and ADI-46158 Fabs 手法: EM (単粒子) / 解像度: 5.6 Å EMDB-43552: CCHFV GP38 bound with ADI-58062 and ADI-63530 Fabs 手法: EM (単粒子) / 解像度: 5.1 Å EMDB-43553: CCHFV GP38 bound with ADI-58026 and ADI-63547 Fabs 手法: EM (単粒子) / 解像度: 4.9 Å 43604 8vww EMDB-43604, PDB-8vww: CCHFV GP38 bound to ADI-46152 and ADI-58048 Fabs 手法: EM (単粒子) / 解像度: 3.9 Å PDB-8vvk: CCHFV GP38 bound to ADI-46143 Fab 手法: X-RAY DIFFRACTION / 解像度: 2.61 Å PDB-8vvl: CCHFV GP38 bound to c13G8 Fab 手法: X-RAY DIFFRACTION / 解像度: 1.8 Å
化合物	ChemComp-HOH: WATER ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-SO4: SULFATE ION / 硫酸ジアニオン ChemComp-CL: Unknown entry / クロリド ChemComp-CO: Unknown entry
由来	homo sapiens (ヒト) crimean-congo hemorrhagic fever virus (ウイルス) crimean-congo hemorrhagic fever virus strain ibar10200 (ウイルス) mus musculus (ハツカネズミ)
キーワード	VIRAL PROTEIN/IMMUNE SYSTEM / CCHFV / GP38 / Antibody / Immunology / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex