Cytotoxic T lymphocytes, also known as CD8+T cells, act a crucial role in regulating viral infection. They let out various toxic substances that can directly lead to the death of viral-infected cells. T cell receptors on cytotoxic T lymphocytes perceive signals given by MHC-Ι–peptide complex, eliminating cells that are responsible for viral replication and thus avoiding the further spread of viruses.
PNAS has recently published an article discussing the role of open reading frame 8 (ORF8) and major histocompatibility complex class Ι (MHC-1) in the T-cell antiviral immunity mechanism of COVID-19. The authors showed that a viral protein of SARS-CoV-2, the ORF8, mediates MHC-Ι down-regulation.
Below are some highlights from the article:
Role of MHC-1 in T-cell antiviral immunity mechanism of COVID-19
- Viral peptides are displayed by MHC-1 molecules in a virus-infected cell
- T-cell receptor on cytotoxic T lymphocytes perceive signal displayed by MHC-Ι–peptide complex
- Cytotoxic T lymphocytes let out various toxic substances that can lead to the death of viral-infected cells, as well as the release of cytokines like interferon-γ, TNF-α, and IL-2
- Cells that are helping viral replication will be eliminated and thus to avoid further spread of viruses
- A restrained antiviral response could cause worsening of symptoms and lengthened recovery
Role of ORF8 in T-cell antiviral immunity mechanism of COVID-19
- ORF8 of SARS-CoV-2 is the only protein that has approximately 20% homology with SARS-CoV
- ORF8 communicates with MHC-Ι molecules and interferes with their down-regulation
- In ORF8-expressing cells, cells infected with SARS-CoV-2 are much less responsive to lysis by cytotoxic T lymphocytes
- Both ORF8- expressing cells and SARS-CoV-2–infected cells were identified to be more resistant to lysis by cytotoxic T lymphocytes
- The down-regulation of MHC-I by SARS-CoV-2 ORF8 is similar to that of HIV-1 Nef in the author’s experimental system
Observations on patients infected with ORF8-defective Δ382 SARS-CoV-2 strain
- Patients infected with ORF8-defective Δ382 SARS-CoV-2 strain exhibited fewer clinical symptoms
- Higher IFN-γ, TNF-α, IL-2, and IL-5 were found in patients infected with ORF8-defective Δ382 SARS-CoV-2 strain is compared to the ones infected with wild-type virus
1. Yiwen Zhang, Yingshi Chen, Yuzhuang Li, Feng Huang, Baohong Luo, Yaochang Yuan, Baijin Xia, Xiancai Ma, Tao Yang, Fei Yu, Jun Liu, Bingfeng Liu, Zheng Song, Jingliang Chen, Shumei Yan, Liyang Wu, Ting Pan, Xu Zhang, Rong Li, Wenjing Huang, Xin He, Fei Xiao, Junsong Zhang, Hui Zhang. The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι. Proceedings of the National Academy of Sciences. 2021 Jun 8.