Cryo-EM structures of #Měnglà virus GP reveal combined #Ebola- and #Marburg-like epitope masking strategies for #antibody evasion

 

Abstract

Ebola virus (EBOV) and Marburg virus (MARV) are highly lethal filoviruses that cause severe hemorrhagic fever in humans. A recently identified bat-borne filovirus, Měnglà virus (MLAV), uses the same NPC1 receptor as EBOV and MARV, raising concerns about its potential cross-species transmission. Here, we report cryo-EM structures of the MLAV surface glycoprotein (GP) in its unbound form and in complex with the MARV-neutralizing antibody MR191. MLAV GP exhibits distinctive structural features in the Wing and heptad repeat 1D (HR1D) regions, retains a visible Cap structure even after protease treatment, and contains a MARV GP-like α2 helix. MR191, a broadly neutralizing marburgvirus antibody that targets the conserved NPC1 receptor-binding pocket in MLAV GP, nonetheless exhibits impaired neutralizing activity, likely due to shielding by the MLAV Cap. In addition, the MLAV mucin-like domain, α2 helix, and HR1A region hinder binding by representative broadly neutralizing ebolavirus antibodies targeting the GP-waist, including 6D6, CA45, ADI-15878, and ADI-15946. Together, these results provide the first structural insights into MLAV GP and identify immune evasion driven by structural and sequence divergence as a major challenge for pan-filovirus antibody development.

Source: 

Link: https://www.pnas.org/doi/abs/10.1073/pnas.2529436123?af=R

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The #Mengla virus (Filoviridae: #Dianlovirus)

 

Abstract

Introduction. 

Filoviruses associated with various species of pteropodid bats (Chiroptera: Pteropodidae) are traditionally regarded as potential causative agents of hemorrhagic fevers with epidemic potential. The known agents of Ebola and Marburg fevers periodically cause sporadic cases and epidemic outbreaks in African countries. Recent discoveries of novel filoviruses associated with pteropodid bats in South and Southeast Asia highlight the necessity to investigate their genetic diversity and pathogenic potential.

The aim of this study was to investigate the genetic diversity and pathogenic potential of new filoviruses associated with bats, based on literature data.

Materials and methods. 

This review is based on an analysis of published literature describing the detection and molecular characterization of novel filoviruses identified in different geographic regions, with a particular focus on filoviruses associated with pteropodid bats in South and Southeast Asia. The analyzed studies include data on virus discovery, genome organization, taxonomic classification, and experimental assessment of biological properties. 

Results. 

Several novel filoviruses have been identified by metagenomic RNA sequencing of tissues from pteropodid bats captured in South and Southeast Asia. Among them, Mengla virus was detected in tissues of pteropodid bats (Rousettus spp.) captured in Mengla County, Yunnan Province, People’s Republic of China. Owing to a high level of genetic divergence, Mengla virus was classified as a representative of a new genus, Dianlovirus, within the family Filoviridae. Although a live isolate of Mengla virus has not yet been obtained, experimental studies using chimeric minigenome systems and virus-like particles suggest that the virus may exhibit tropism for tissues of various vertebrate hosts, including humans.

Conclusion. 

Members of the family Filoviridae are widely distributed within the geographic range of their natural reservoir–pteropodid bats–across South and Southeast Asia, including viruses evolutionarily related to Ebola and Marburg viruses. Although human disease caused by Mengla virus and other recently discovered filoviruses has not been documented, the potential for cross-species transmission and the emergence of novel filovirus infections in endemic regions remains.

Source: 

Link: https://virusjour.crie.ru/jour/article/view/16805

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