The viral fitness and intrinsic pathogenicity of dominant SARS-CoV-2 Omicron sublineages BA.1, BA.2, and BA.5

Shuai, Huiping; Chan, Jasper Fuk‐Woo; Hu, Bingjie; Chai, Yue; Yoon, Chaemin; Liu, Huan; Liu, Yuanchen; Shi, Jialu; Zhu, Tianrenzheng; Hu, Jing-Chu; Hu, Ye-Fan; Hou, Yuxin; Huang, Xiner; Yuen, Terrence Tsz‐Tai; Wang, Yan; Zhang, Jinjin; Xia, Yao; Chen, Lin-Lei; Cai, Jian‐Piao; Zhang, Anna Jinxia; Yuan, Shuofeng; Zhou, Jie; Zhang, Baozhong; Huang, Jian‐Dong; Yuen, Kwok‐Yung; To, Kelvin Kai-Wang; Chu, Hin

doi:10.1016/j.ebiom.2023.104753

Cited by 24 publications

(14 citation statements)

References 49 publications

(92 reference statements)

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“…During the manuscript preparation, several studies on the characteristics of BA.5 and BA.2.75 have emerged. In general, research in different animal models supports the enhanced infectivity and replicability of BA.5 in nasal turbinate and lungs compared to BA.1 and BA.2 51–53 . Conversely, BA.2.75 exhibits greater infectivity and pathogenicity in human lung cells and hamster lungs compared to BA.5, along with more robust immune evasion 20,22,23 .…”

Section: Discussionmentioning

confidence: 88%

“…In general, research in different animal models supports the enhanced infectivity and replicability of BA.5 in nasal turbinate and lungs compared to BA.1 and BA.2. [51][52][53] Conversely, BA.2.75 exhibits greater infectivity and pathogenicity in human lung cells and hamster lungs compared to BA.5, along with more robust immune evasion. 20,22,23 Our findings align with these reports, underscoring the heightened infectivity and pathogenicity of BA.5 compared to earlier Omicron strains.…”

Section: Discussionmentioning

confidence: 99%

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Differential pathogenic and molecular features in neurological infection of SARS‐CoV‐2 Omicron BA.5.2 and BA.2.75 and Delta

Wang,

Yang,

et al. 2024

Journal of Medical Virology

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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 variants of SARS‐CoV‐2, Omicron BA.2.75 and BA.5, led to global infection peaks between May 2022 and May 2023, yet their precise characteristics in pathogenesis are not well understood. In this study, we compared these two Omicron sublineages with the previously dominant Delta variant using a human angiotensin‐converting enzyme 2 knock‐in mouse model. As expected, Delta exhibited higher viral replication in the lung and brain than both Omicron sublineages which induced less severe lung damage and immune activation. In contrast, the Omicron variants especially BA.5.2 showed a propensity for cellular proliferation and developmental pathways. Both Delta and BA.5.2 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.5.2 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.5.2 demonstrating enhanced immune evasion and neural damage that could exacerbate neurological sequelae.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Differential pathogenic and molecular features in neurological infection of SARS‐CoV‐2 Omicron BA.5.2 and BA.2.75 and Delta

Wang,

Yang,

et al. 2024

Journal of Medical Virology

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“…In contrast, Cathepsins become involved when the virus enters cells via the endosomal pathway and fusion is triggered by the acidic environment of the endosome. Notably, it has been reported that the less efficient Spike cleavage of Omicron BA.1 Spike at S1/S2 is associated with reduced dependency on TMPRSS2 and a shift toward Cathepsin-dependent endosomal entry [ 66 , 67 ]. This shift in cellular tropism away from TMPRSS2-expressing cells is largely mediated by a H655Y substitution in Spike and may impact viral pathogenesis [ 38 , 66 , 68 ].…”

Section: Early Features Of the Sars-cov-2 Spike Proteinmentioning

confidence: 99%

Causes and Consequences of Coronavirus Spike Protein Variability

Zech,

Jung,

Jacob

et al. 2024

Viruses

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Coronaviruses are a large family of enveloped RNA viruses found in numerous animal species. They are well known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in the human population. In contrast the most recent human hCoV, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we briefly address the significance and perspectives of broad-spectrum therapeutics and vaccines.

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“…The coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) resulted in over 772 million confirmed cases and more than 6 million deaths globally 1 . While the pandemic phase of SARS‐CoV‐2 is considered over, the latest variant of the concern of the virus, SARS‐CoV‐2 Omicron, has evolved to robustly escape the host adaptive immune response while gained a replication fitness in the upper respiratory tract 2–7 . These unique features of Omicron have allowed the virus to continuously circulate in the human population.…”

Section: Introductionmentioning

confidence: 99%

“…1 While the pandemic phase of SARS-CoV-2 is considered over, the latest variant of the concern of the virus, SARS-CoV-2 Omicron, has evolved to robustly escape the host adaptive immune response while gained a replication fitness in the upper respiratory tract. [2][3][4][5][6][7] These unique features of Omicron have allowed the virus to continuously circulate in the human population. Interferon (IFN) signaling plays critical roles in COVID-19 pathogenesis and interventions.…”

Section: Introductionmentioning

confidence: 99%

Type‐II IFN inhibits SARS‐CoV‐2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3‐dioxygenase‐mediated pathways

Yang,

Chan,

Yoon

et al. 2024

Journal of Medical Virology

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Interferons (IFNs) are critical for immune defense against pathogens. While type‐I and ‐III IFNs have been reported to inhibit SARS‐CoV‐2 replication, the antiviral effect and mechanism of type‐II IFN against SARS‐CoV‐2 remain largely unknown. Here, we evaluate the antiviral activity of type‐II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS‐CoV‐2 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFNγ treatment does not significantly modulate the expression of SARS‐CoV‐2 entry‐related factors and induces a similar level of pro‐inflammatory response in human lung tissues when compared with IFNβ treatment. Mechanistically, we show that overexpression of indoleamine 2,3‐dioxygenase 1 (IDO1), which is most profoundly induced by IFNγ, substantially restricts the replication of ancestral SARS‐CoV‐2 and the Alpha and Delta variants. Meanwhile, loss‐of‐function study reveals that IDO1 knockdown restores SARS‐CoV‐2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l‐tryptophan, a substrate of IDO1, partially rescues the IFNγ‐mediated inhibitory effect on SARS‐CoV‐2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type‐II IFN potently inhibits SARS‐CoV‐2 replication through IDO1‐mediated antiviral response.

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The viral fitness and intrinsic pathogenicity of dominant SARS-CoV-2 Omicron sublineages BA.1, BA.2, and BA.5

Cited by 24 publications

References 49 publications

Differential pathogenic and molecular features in neurological infection of SARS‐CoV‐2 Omicron BA.5.2 and BA.2.75 and Delta

Differential pathogenic and molecular features in neurological infection of SARS‐CoV‐2 Omicron BA.5.2 and BA.2.75 and Delta

Causes and Consequences of Coronavirus Spike Protein Variability

Type‐II IFN inhibits SARS‐CoV‐2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3‐dioxygenase‐mediated pathways

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