Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants

Moriyama, Miyu; Lucas, Carolina; Monteiro, Valter Silva; Iwasaki, Akiko; Chen, Nicholas; Breban, Mallery I.; Hahn, Anne M.; Pham, Kien; Koch, Tobias R.; Chaguza, Chrispin; Tikhonova, Irina; Castaldi, Christopher; Mane, Shrikant; Kumar, Bony De; Ferguson, David; Kerantzas, Nicholas; Peaper, David R.; Landry, Marie L.; Schulz, Wade; Vogels, Chantal B.F.; Grubaugh, Nathan D.

doi:10.1073/pnas.2221652120

Cited by 24 publications

(7 citation statements)

References 68 publications

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“…To successfully establish infection and replicate in the host, Omicron variants have acquired the ability to inhibit MHC-I processing and the presentation of viral antigens. For example, Omocron variant ORF8 (open reading frame 8) protein induces autophagic degradation of MHC-I and confers resistance to CTL surveillance (92). These findings suggest that during Omicron infection, defective stimulation of MHC-I genetic expression in airways and epithelial cells from the intestines impairs cellular immunity mediated by CD8 + T cells (93).…”

Section: Other Immune Evasion Mechanisms Of Omicron Variantsmentioning

confidence: 99%

Potential immune evasion of the severe acute respiratory syndrome coronavirus 2 Omicron variants

Chen,

He,

Liu

et al. 2024

Front. Immunol.

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Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic. The Omicron variant (B.1.1.529) was first discovered in November 2021 in specimens collected from Botswana, South Africa. Omicron has become the dominant variant worldwide, and several sublineages or subvariants have been identified recently. Compared to those of other mutants, the Omicron variant has the most highly expressed amino acid mutations, with almost 60 mutations throughout the genome, most of which are in the spike (S) protein, especially in the receptor-binding domain (RBD). These mutations increase the binding affinity of Omicron variants for the ACE2 receptor, and Omicron variants may also lead to immune escape. Despite causing milder symptoms, epidemiological evidence suggests that Omicron variants have exceptionally higher transmissibility, higher rates of reinfection and greater spread than the prototype strain as well as other preceding variants. Additionally, overwhelming amounts of data suggest that the levels of specific neutralization antibodies against Omicron variants decrease in most vaccinated populations, although CD4+ and CD8+ T-cell responses are maintained. Therefore, the mechanisms underlying Omicron variant evasion are still unclear. In this review, we surveyed the current epidemic status and potential immune escape mechanisms of Omicron variants. Especially, we focused on the potential roles of viral epitope mutations, antigenic drift, hybrid immunity, and “original antigenic sin” in mediating immune evasion. These insights might supply more valuable concise information for us to understand the spreading of Omicron variants.

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Section: Other Immune Evasion Mechanisms Of Omicron Variantsmentioning

confidence: 99%

Potential immune evasion of the severe acute respiratory syndrome coronavirus 2 Omicron variants

Chen,

He,

Liu

et al. 2024

Front. Immunol.

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“…While a recent study identified HLA-B*15 expression and previous coronavirus exposure as a determinant of rapid SARS-CoV-2 clearance and asymptomatic infection, this involved only 17-25% of asymptomatic patients (Augusto et al, 2023). The ability of SARS-CoV-2 to downregulate HLA-B suggests that other important immune mechanisms enabling SARS-CoV-2 clearance may be at play in the human lung (Moriyama et al, 2023; Yoo et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

A Novel Human Extravascular Monocyte Subset with Antiviral Functions Is Crucial for Resolving Lung Tissue Infection

Kenney,

O’Connell,

Tseng

et al. 2024

Preprint

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The lung-resident immune mechanisms driving resolution of SARS-CoV-2 infection in humans remain elusive. Using mice co-engrafted with a genetically matched human immune system and fetal lung xenograft (fLX), we mapped the immunological events defining resolution of SARS-CoV-2 infection in human lung tissues. Viral infection is rapidly cleared from fLX following a peak of viral replication. Acute replication results in the emergence of cell subsets enriched in viral RNA, including extravascular inflammatory monocytes (iMO) and macrophage-like T-cells, which dissipate upon infection resolution. iMO display robust antiviral responses, are transcriptomically unique among myeloid lineages, and their emergence associates with the recruitment of circulating CD4+ monocytes. Consistently, mice depleted for human CD4+ cells but not CD3+ T-cells failed to robustly clear infectious viruses and displayed signatures of chronic infection. Our findings uncover the transient differentiation of extravascular iMO from CD4+ monocytes as a major hallmark of SARS-CoV-2 infection resolution and open avenues for unravelling viral and host adaptations defining persistently active SARS-CoV-2 infection.

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“…For example, the human immunodeficiency virus 1 Nef protein diverts pMHC-I complexes to the protein degradation pathway [ 37 , 38 ], and infection with influenza A and B viruses also suppresses surface MHC-I expression [ 39 ]. SARS-CoV-2 infection was shown to disrupt MHC-I cell surface expression [ 40 , 41 ], in part, by disrupting nuclear transport of NLRC5 [ 41 ], the principal MHC-I transcription factor.…”

Section: Introductionmentioning

confidence: 99%

Chikungunya virus infection disrupts MHC-I antigen presentation via nonstructural protein 2

Ware,

Parks,

da Silva

et al. 2024

PLoS Pathog

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Infection by chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes severe polyarthralgia and polymyalgia, which can last in some people for months to years. Chronic CHIKV disease signs and symptoms are associated with the persistence of viral nucleic acid and antigen in tissues. Like humans and nonhuman primates, CHIKV infection in mice results in the development of robust adaptive antiviral immune responses. Despite this, joint tissue fibroblasts survive CHIKV infection and can support persistent viral replication, suggesting that they escape immune surveillance. Here, using a recombinant CHIKV strain encoding the fluorescent protein VENUS with an embedded CD8+ T cell epitope, SIINFEKL, we observed a marked loss of both MHC class I (MHC-I) surface expression and antigen presentation by CHIKV-infected joint tissue fibroblasts. Both in vivo and ex vivo infected joint tissue fibroblasts displayed reduced cell surface levels of H2-Kb and H2-Db MHC-I proteins while maintaining similar levels of other cell surface proteins. Mutations within the methyl transferase-like domain of the CHIKV nonstructural protein 2 (nsP2) increased MHC-I cell surface expression and antigen presentation efficiency by CHIKV-infected cells. Moreover, expression of WT nsP2 alone, but not nsP2 with mutations in the methyltransferase-like domain, resulted in decreased MHC-I antigen presentation efficiency. MHC-I surface expression and antigen presentation was rescued by replacing VENUS-SIINFEKL with SIINFEKL tethered to β2-microglobulin in the CHIKV genome, which bypasses the requirement for peptide processing and TAP-mediated peptide transport into the endoplasmic reticulum. Collectively, this work suggests that CHIKV escapes the surveillance of antiviral CD8+ T cells, in part, by nsP2-mediated disruption of MHC-I antigen presentation.

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Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants

Cited by 24 publications

References 68 publications

Potential immune evasion of the severe acute respiratory syndrome coronavirus 2 Omicron variants

Potential immune evasion of the severe acute respiratory syndrome coronavirus 2 Omicron variants

A Novel Human Extravascular Monocyte Subset with Antiviral Functions Is Crucial for Resolving Lung Tissue Infection

Chikungunya virus infection disrupts MHC-I antigen presentation via nonstructural protein 2

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