PXD042841-1

PXD042841 is an original dataset announced via ProteomeXchange.

Title	Attenuated pathogenicity coupled with novel features of SARS-CoV-2 Omicron BA.2.75 and BA.5 variants
Description	The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global threat, exacerbated by the emergence of viral variants. Two recent variants of SARS-CoV-2, Omicron BA.2.75 and BA.5, have been reported globally, yet their precise characteristics are not well understood. In this study, we compared these two Omicron sub-lineages with the previously dominant Delta variant using a hACE2 knock-in mouse model. As expected, Delta exhibited higher viral replication in the lung and brain than both Omicron sub-lineages that induced less severe lung damage and immune activation. In contrast, the Omicron variants especially BA.5 showed a propensity for cellular proliferation and developmental pathways. Both Delta and BA.5 variants, but not BA.2.75, led to decreased pulmonary lymphocytes, indicating differential adaptive immune response. Neuroinvasiveness was shared with all strains, accompanied by vascular abnormalities, synaptic injury, and loss of astrocytes. However, Immunostaining assays and transcriptomic analysis showed that BA.5 displayed stronger immune suppression and neurodegeneration, while BA.2.75 exhibited more similar characteristics to Delta in the cortex. Such differentially infectious features could be partially attributed to the weakened interaction between Omicron Spike protein and host proteomes decoded via co-immunoprecipitation followed by mass spectrometry in neuronal cells. Our present study supports attenuated replication and pathogenicity of Omicron variants but also highlights their newly infectious characteristics in the lung and brain, especially with BA.5 demonstrating enhanced immune evasion and neural damage that could exacerbate neurological sequelae.
HostingRepository	iProX
AnnounceDate	2023-06-09
AnnouncementXML	Submission_2024-06-04_20:02:23.667.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Erlin Wang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-09 03:11:13	ID requested
⏵ 1	2024-06-04 20:02:24	announced

Dataset with its publication pending

submitter keyword: SARS-Cov-2, hACE2 mice, BA.5, BA.2.75, Delta.

Jianxiong Zeng
contact affiliation	Kunming Institute of Zoology
contact email	zengjianxiong@mail.kiz.ac.cn
lab head
Erlin Wang
contact affiliation	Kunming Institute of Zoology
contact email	wangerlin@mail.kiz.ac.cn
dataset submitter

iProX dataset URI