Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
LY6E Restricts Entry of Human Coronaviruses, Including Currently Pandemic SARS-CoV-2
Journal of virology, v 94(18)
31 Aug 2020
PMID: 32641482
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
C3A is a subclone of the human hepatoblastoma HepG2 cell line with strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2), gamma-interferon-inducible lysosome/endosome-localized thiolreductase (GILT), and lymphocyte antigen 6 family member E (LY6E), the three cellular proteins identified to function in interference with virus entry, were expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-O43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFN-inducible transmembrane 3 (IFITM3) restriction of human coronavirus (CoV) entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis via a mechanism distinct from other factors that modulate CoV entry.
Virus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control of host innate and adaptive immune responses. In the last decade, several interferon-inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH, and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as a host factor that facilitates the entry of several human-pathogenic viruses, including human immunodeficiency virus, influenza A virus, and yellow fever virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection.
Metrics
Details
- Title
- LY6E Restricts Entry of Human Coronaviruses, Including Currently Pandemic SARS-CoV-2
- Creators
- Xuesen Zhao - Baruch S. Blumberg InstituteShuangli Zheng - Beijing Key Laboratory of Emerging Infectious Disease, Beijing, ChinaDanying Chen - Beijing Key Laboratory of Emerging Infectious Disease, Beijing, ChinaMei Zheng - Beijing Key Laboratory of Emerging Infectious Disease, Beijing, ChinaXinglin Li - Beijing Key Laboratory of Emerging Infectious Disease, Beijing, ChinaGuoli Li - Beijing Key Laboratory of Emerging Infectious Disease, Beijing, ChinaHanxin Lin - University of LondonJinhong Chang - Baruch S. Blumberg InstituteHui Zeng - Beijing Key Laboratory of Emerging Infectious Disease, Beijing, ChinaJu-Tao Guo - Baruch S. Blumberg Institute
- Publication Details
- Journal of virology, v 94(18)
- Publisher
- American Society for Microbiology (ASM)
- Grant note
- R01 AI113267 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000568836000007
- Scopus ID
- 2-s2.0-85090148097
- Other Identifier
- 991020547323204721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Virology