Identification of adipocyte plasma membrane-associated protein as a novel modulator of human cytomegalovirus infection

Xiaohua Ye, Xun Gui, Daniel C. Freed, Zhiqiang Ku, Leike Li, Yuanzhi Chen, Wei Xiong, Xuejun Fan, Hang Su, Xi He, Richard R. Rustandi, John W. Loughney, Ningning Ma, Amy S. Espeseth, Jian Liu, Hua Zhu, Dai Wang, Ningyan Zhang, Tong Ming Fu, Zhiqiang An

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause disability in newborns and serious clinical diseases in immunocompromised patients. HCMV has a large genome with enormous coding potential; its viral particles are equipped with complicated glycoprotein complexes and can infect a wide range of human cells. Although multiple host cellular receptors interacting with viral glycoproteins have been reported, the mechanism of HCMV infection remains a mystery. Here we report identification of adipocyte plasma membrane-associated protein (APMAP) as a novel modulator active in the early stage of HCMV infection. APMAP is necessary for HCMV infection in both epithelial cells and fibroblasts; knockdown of APMAP expression significantly reduced HCMV infection of these cells. Interestingly, ectopic expression of human APMAP in cells refractory to HCMV infection, such as canine MDCK and murine NIH/3T3 cells, promoted HCMV infection. Furthermore, reduction in viral immediate early (IE) gene transcription at 6 h post infection and delayed nucleus translocation of tegument delivered pp65 at 4 h post infection were detected in APMAP-deficient cells but not in the wildtype cells. These results suggest that APMAP plays a role in the early stage of HCMV infection. Results from biochemical studies of APMAP and HCMV proteins suggest that APMAP could participate in HCMV infection through interaction with gH/gL containing glycoprotein complexes at low pH and mediate nucleus translocation of tegument pp65. Taken together, our results suggest that APMAP functions as a modulator promoting HCMV infection in multiple cell types and is an important player in the complex HCMV infection mechanism.

Original languageEnglish (US)
Article numbere1007914
JournalPLoS pathogens
Volume15
Issue number7
DOIs
StatePublished - Jul 2019

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Fingerprint

Dive into the research topics of 'Identification of adipocyte plasma membrane-associated protein as a novel modulator of human cytomegalovirus infection'. Together they form a unique fingerprint.

Cite this