更新于：2024-11-01

PUUV glycoprotein

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 PUUV glycoprotein 相关的药物

ADI-42898

靶点

PUUV glycoprotein

作用机制

PUUV glycoprotein 抑制剂

在研机构

Albert Einstein College of Medicine, Inc. [+4]

原研机构

Albert Einstein College of Medicine, Inc. [+3]

在研适应症

汉坦病毒感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PUUV glycoprotein 相关的临床结果

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100 项与 PUUV glycoprotein 相关的转化医学

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0 项与 PUUV glycoprotein 相关的专利（医药）

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项与 PUUV glycoprotein 相关的文献（医药）

2023-10-01·The Journal of general virology

Validation of an antigenic site targeted by monoclonal antibodies against Puumala virus.

Article

作者: Iheozor-Ejiofor, Rommel Paneth ; Lundkvist, Åke ; Levanov, Lev ; Rissanen, Ilona ; Kedari, Ashwini ; Plyusnin, Alexander ; Vapalahti, Olli

Identification of B-cell epitopes facilitates the development of vaccines, therapeutic antibodies and diagnostic tools. Previously, the binding site of the bank vole monoclonal antibody (mAb) 4G2 against Puumala virus (PUUV, an orthohantavirus in the Hantaviridae family of the Bunyavirales order) was predicted using a combination of methods, including pepscan, phage-display, and site-directed mutagenesis of vesicular stomatitis virus (VSV) particles pseudotyped with Gn and Gc glycoproteins from PUUV. These techniques led to the identification of the neutralization escape mutation F915A. To our surprise, a recent crystal structure of PUUV Gc in complex with Fab 4G2 revealed that residue F915 is distal from epitope of mAb 4G2. To clarify this issue and explore potential explanations for the inconsistency, we designed a mutagenesis experiment to probe the 4G2 epitope, with three PUUV pseudoviruses carrying amino acid changes E725A, S944F, and S946F, located within the structure-based 4G2 epitope on the Gc. These amino acid changes were able to convey neutralization escape from 4G2, and S944F and S946F also conveyed escape from neutralization by human mAb 1C9. Furthermore, our mapping of all the known neutralization evasion sites from hantaviral Gcs onto PUUV Gc revealed that over 60 % of these sites reside within or close to the epitope of mAb 4G2, indicating that this region may represent a crucial area targeted by neutralizing antibodies against PUUV, and to a lesser extent, other hantaviruses. The identification of this site of vulnerability could guide the creation of subunit vaccines against PUUV and other hantaviruses in the future.

2019-01-01·Virus Research3区 · 医学

Virus- and cell type-specific effects in orthohantavirus infection

3区 · 医学

Article

作者: Hägele, Stefan ; Nusshag, Christian ; Müller, Alexander ; Zeier, Martin ; Reiser, Jochen ; Krautkrämer, Ellen

Orthohantaviruses Hantaan (HTNV) and Puumala (PUUV) virus cause hemorrhagic fever with renal syndrome (HFRS), that is characterized by acute renal failure with often massive proteinuria and by morphological changes of the tubular and glomerular apparatus. Orthohantaviral N protein is found in renal cells and plays a key role in replication. However, the replication in human renal cells is not well characterized. Therefore, we examined the orthohantaviral infection in different human renal cells. Differences in localization of N protein, release of particles, and modulation of the actin cytoskeleton between both virus species are observed in human renal cells. A substantial portion of HTNV N protein demonstrates a filamentous pattern in addition to the typical punctate pattern. Release of HTNV depends on an intact actin and microtubule cytoskeleton. In contrast, PUUV N protein is generally localized in a punctate pattern and release of PUUV does not require an intact actin cytoskeleton. Infection of podocytes results in cytoskeletal rearrangements that are more pronounced for HTNV. Analyzing Vero E6 cells revealed differences compared to human renal cells. The pattern of N proteins is strictly punctate, release does not depend on an intact actin cytoskeleton and cytoskeletal rearrangements are not present. No virus-specific variations between HTNV and PUUV are observed in Vero E6 cells. Using human renal cells as cell culture model for orthohantavirus infection demonstrates virus-specific differences and orthohantavirus-induced cytoskeletal rearrangements that are not observed in Vero E6 cells. Therefore, the choice of an appropriate cell culture system is a prerequisite to study orthohantavirus pathogenicity.

PLOS Pathogens1区 · 医学

Crystal Structure of Glycoprotein C from a Hantavirus in the Post-fusion Conformation

1区 · 医学

ArticleOA

作者: Tischler, Nicole D ; Willensky, Shmuel ; Dessau, Moshe ; Bignon, Eduardo A ; Modis, Yorgo ; Bar-Rogovsky, Hagit

Hantaviruses are important emerging human pathogens and are the causative agents of serious diseases in humans with high mortality rates. Like other members in the Bunyaviridae family their M segment encodes two glycoproteins, GN and GC, which are responsible for the early events of infection. Hantaviruses deliver their tripartite genome into the cytoplasm by fusion of the viral and endosomal membranes in response to the reduced pH of the endosome. Unlike phleboviruses (e.g. Rift valley fever virus), that have an icosahedral glycoprotein envelope, hantaviruses display a pleomorphic virion morphology as GN and GC assemble into spikes with apparent four-fold symmetry organized in a grid-like pattern on the viral membrane. Here we present the crystal structure of glycoprotein C (GC) from Puumala virus (PUUV), a representative member of the Hantavirus genus. The crystal structure shows GC as the membrane fusion effector of PUUV and it presents a class II membrane fusion protein fold. Furthermore, GC was crystallized in its post-fusion trimeric conformation that until now had been observed only in Flavi- and Togaviridae family members. The PUUV GC structure together with our functional data provides intriguing evolutionary and mechanistic insights into class II membrane fusion proteins and reveals new targets for membrane fusion inhibitors against these important pathogens.