Ebola virus exploits a monocyte differentiation program to promote its entry

Osvaldo Martinez, Joshua C. Johnson, Anna Honko, Benjamin Yen, Reed S. Shabman, Lisa E. Hensley, Gene G. Olinger, Christopher F. Basler

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Antigen-presenting cells (APCs) are critical targets of Ebola virus (EBOV) infection in vivo. However, the susceptibility of monocytes to infection is controversial. Studies indicate productive monocyte infection, and yet monocytes are also reported to be resistant to EBOV GP-mediated entry. In contrast, monocyte-derived macrophages and dendritic cells are permissive for both EBOV entry and replication. Here, freshly isolated monocytes are demonstrated to indeed be refractory to EBOV entry. However, EBOV binds monocytes, and delayed entry occurs during monocyte differentiation. Cultured monocytes spontaneously downregulate the expression of viral entry restriction factors such as interferon-inducible transmembrane proteins, while upregulating the expression of critical EBOV entry factors cathepsin B and NPC1. Moreover, these processes are accelerated by EBOV infection. Finally, ectopic expression of NPC1 is sufficient to rescue entry into an undifferentiated, normally nonpermissive monocytic cell line. These results define the molecular basis for infection of APCs and suggest means to limit APC infection.

Original languageEnglish
Pages (from-to)3801-3814
Number of pages14
JournalJournal of Virology
Volume87
Issue number7
DOIs
StatePublished - Apr 2013

Fingerprint

Dive into the research topics of 'Ebola virus exploits a monocyte differentiation program to promote its entry'. Together they form a unique fingerprint.

Cite this