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

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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Ye X,Gui X,Freed DC,Ku Z,Li L,Chen Y,Xiong W,Fan X,Su H,He X,Rustandi RR,Loughney JW,Ma N,Espeseth AS,Liu J,Zhu H,Wang D,Zhang N,Fu TM,An Z

doi

10.1371/journal.ppat.1007914

subject

Has Abstract

pub_date

2019-07-29 00:00:00

pages

e1007914

issue

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-19-00382

journal_volume

pub_type

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