The host mannose-6-phosphate pathway and viral infection

Front Cell Infect Microbiol. 2024 Jan 31:14:1349221. doi: 10.3389/fcimb.2024.1349221. eCollection 2024.


Viruses, despite their simple structural composition, engage in intricate and complex interactions with their hosts due to their parasitic nature. A notable demonstration of viral behavior lies in their exploitation of lysosomes, specialized organelles responsible for the breakdown of biomolecules and clearance of foreign substances, to bolster their own replication. The man-nose-6-phosphate (M6P) pathway, crucial for facilitating the proper transport of hydrolases into lysosomes and promoting lysosome maturation, is frequently exploited for viral manipulation in support of replication. Recently, the discovery of lysosomal enzyme trafficking factor (LYSET) as a pivotal regulator within the lysosomal M6P pathway has introduced a fresh perspective on the intricate interplay between viral entry and host factors. This groundbreaking revelation illuminates unexplored dimensions of these interactions. In this review, we endeavor to provide a thorough overview of the M6P pathway and its intricate interplay with viral factors during infection. By consolidating the current understanding in this field, our objective is to establish a valuable reference for the development of antiviral drugs that selectively target the M6P pathway.

Keywords: GNPT; LYSET; M6P; M6PR; cathepsin; infectious diseases; lysosome; virus.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Hydrolases* / metabolism
  • Lysosomes / metabolism
  • Mannosephosphates / analysis
  • Mannosephosphates / chemistry
  • Mannosephosphates / metabolism
  • Virus Diseases* / metabolism


  • mannose-6-phosphate
  • Hydrolases
  • Mannosephosphates

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (32070718), the Shenzhen Bay Laboratory Open Fund Project (SZBL2021080601003), the State Key Laboratory of Respiratory Disease (SKLRD) Open Project SKLRD-Z-202115 and Guangzhou Key Medical Discipline Construction Project Fund.