ZDHHC11 Suppresses Zika Virus Infections by Palmitoylating the Envelope Protein

Viruses. 2023 Jan 2;15(1):144. doi: 10.3390/v15010144.

Abstract

Zika virus (ZIKV) is an RNA-enveloped virus that belongs to the Flavivirus genus, and ZIKV infections potentially induce severe neurodegenerative diseases and impair male fertility. Palmitoylation is an important post-translational modification of proteins that is mediated by a series of DHHC-palmitoyl transferases, which are implicated in various biological processes and viral infections. However, it remains to be investigated whether palmitoylation regulates ZIKV infections. In this study, we initially observed that the inhibition of palmitoylation by 2-bromopalmitate (2-BP) enhanced ZIKV infections, and determined that the envelope protein of ZIKV is palmitoylated at Cys308. ZDHHC11 was identified as the predominant enzyme that interacts with the ZIKV envelope protein and catalyzes its palmitoylation. Notably, ZDHHC11 suppressed ZIKV infections in an enzymatic activity-dependent manner and ZDHHC11 knockdown promoted ZIKV infection. In conclusion, we proposed that the envelope protein of ZIKV undergoes a novel post-translational modification and identified a distinct mechanism in which ZDHHC11 suppresses ZIKV infections via palmitoylation of the ZIKV envelope protein.

Keywords: 2-BP; ZDHHC11; Zika virus; envelope protein; palmitoylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / metabolism
  • Flavivirus* / metabolism
  • Humans
  • Male
  • Proteins / metabolism
  • Viral Envelope Proteins / metabolism
  • Zika Virus Infection*
  • Zika Virus* / physiology

Substances

  • Antibodies, Viral
  • Proteins
  • Viral Envelope Proteins
  • ZDHHC11 protein, human

Grants and funding

This research was funded by: the National Nature Science Foundation of China, grant number 81973549 and U22A20335; the Key-Area Research and Development Program of Guangdong Province, grant number 2020B1111100002; and Guangzhou University of Chinese Medicine First-Class Universities and Top Disciplines Scientific Research Team Projects, grant number 2021XK16.