Can coronavirus SARS-CoV-2 invade T cells?

A recent paper published by Wang et al.  suggest that this is the case.

The SARS-CoV-2 (COVID-19) virus uses the human angiotensin-converting enzyme 2 (ACE2) as the receptor for its entry into cells. However, Wang et al. recently reported that the virus could also enter T lymphocytes through the receptor-mediated endocytosis pathway.

The recently published data of this research group suggests that SARS-CoV-2 can infect T cells through S protein-mediated membrane fusion. Wang et al. proposed CD147, which is present on the surface of T lymphocytes, as an additional cell entry route for SARS-CoV-2.

Many pathogenic infections utilize CD147. These include infections by human immunodeficiency virus (HIV), hepatitis B (HBV) and C viruses (HCV), and Kaposi’s sarcoma-associated herpesvirus (KSHV).

CD147 or EMMPRIN is a member of the immunoglobin superfamily in humans. The term CD147 refers to Cluster of Differentiation 147 or Extracellular Matrix Metallo-Proteinase INducer (EMMPRIN), which is a transmembrane glycoprotein encoded by the basigin gene, also known as basigin (BSG). CD147 plays a role in intercellular recognition that as a type I integral membrane receptor has many ligands.  Many tissues and cells express this glycoprotein.
 Furthermore, CD147 also plays a significant role in the progression of many cancers since the protein regulates cell proliferation, apoptosis, tumor cell migration, metastasis and differentiation, and stimulates the secretion of metalloproteinases and cytokines.


Figure 1:  Solution structure of the IgI domain CD147, PDB ID 5XF0.  The secondary structure model of the molecule is shown to the left, the cartoon model in the middle, and the surface model at the right part of the image.


Figure 2:  Crystal structure of the IgI domain CD147, PDB ID 3B5H.  The secondary structure model of the molecule is shown to the left, the cartoon model in the middle, and the surface model at the right part of the image.

The hepatocellular carcinoma (HCC)-associated antigen and the HAb18G/CD147 protein stimulate adjacent fibroblasts and HCC cells to produce elevated levels of several matrix metalloproteinases (Yu et al.). Furthermore, CD147 also facilitates invasion and metastasis of HCC cells. Therefore, Yu et al. suggested that HAb18G/CD147 is a universal cancer biomarker for diagnosis and prognostic assessment of a wide range of cancers.

For studying the biological function of CD147, for example, for epitope mapping, peptide libraries derived from the protein sequence allow elucidating important binding partners of the protein. 


He B, Mao C, Ru B, Han H, Zhou P, Huang J. Epitope mapping of metuximab on CD147 using phage display and molecular docking. Comput Math Methods Med. 2013;2013:983829. [PMC]

Jin S, Ding P, Chu P, Li H, Sun J, Liang D, Song F, Xia B. Zn(II) can mediate self-association of the extracellular C-terminal domain of CD147. Protein Cell. 2018 Mar;9(3):310-315. [Article]

Pushkarsky T, Zybarth G, Dubrovsky L, Yurchenko V, Tang H, Guo H, Toole B, Sherry B, Bukrinsky M. CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6360-5. [PMC]

Wang, X., Xu, W., Hu, G. et al.; SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cell Mol Immunol (2020). [Nature]

Xia, S. et al. Inhibition of SARS-CoV-2 infection (previously 2019-nCoV) by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. https://doi.org/10.1038/s41422-020-0305-x (2020). [PubMed] [Nature]

Xiong L, Edwards CK 3rd, Zhou L. The biological function and clinical utilization of CD147 in human diseases: a review of the current scientific literature. Int J Mol Sci. 2014 Sep 29;15(10):17411-41. [PMC]

Yu XL, Hu T, Du JM, Ding JP, Yang XM, Zhang J, Yang B, Shen X, Zhang Z, Zhong WD, et al.; Crystal structure of HAb18G/CD147: implications for immunoglobulin superfamily homophilic adhesion. J Biol Chem. 2008;283:18056–18065. [JBC]

Bio-Synthesis Inc. is pleased to offer a large variety of oligonucleotides and peptides for a number of research applications, including COVID 19 testing, analysis and vaccine development!