Autophagy facilitates antibody-enhanced dengue virus infection in human pre-basophil/mast cells

Yi Ting Fang, Shu Wen Wan, Yi Tien Lu, Ju Han Yao, Chiou Feng Lin, Li Jin Hsu, Michael G. Brown, Jean S. Marshall, Robert Anderson, Yee Shin Lin

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Dengue virus (DENV) infection can cause severe hemorrhagic disease in humans. Although the pathogenic mechanisms underlying severe DENV disease remain unclear, one of the possible contributing factors is antibody-dependent enhancement (ADE) which occurs when sub-neutralizing antibodies derived from a previous DENV infection enhance viral infection through interaction between virus-antibody complexes and FcR-bearing cells, such as macrophages and basophil/mast cells. Although recent reports showed that DENV induces autophagy, the relationship between antibody-enhanced DENV infection and autophagy is not clear. Methodology/Principal Findings: We showed that sub-neutralizing antibodies derived from dengue patient sera enhanced DENV infection and autophagy in the KU812 pre-basophil-like cell line as well as the HMC-1 immature mast cell line. Antibody-enhanced DENV infection of KU812 cells increased the number of autophagosome vesicles, LC3 punctation, LC3-II accumulation, and p62 degradation over that seen in cells infected with DENV alone. The percentages of DENV envelope (E) protein-positive cells and LC3 puncta following antibody-enhanced DENV infection of KU812 cells were reduced by the autophagy inhibitor 3-MA. Antibody-enhanced DENV infection of HMC-1 cells showed co-localization of DENV E protein and dsRNA with autophagosomes, which was inhibited by 3-MA treatment. Furthermore, DENV infection and replication were reduced when KU812 cells were transfected with the autophagy-inhibiting Atg4BC74A mutant. Conclusions/Significance: Our results demonstrate a significant induction of autophagy in antibody-enhanced DENV infection of pre-basophil-like KU812 and immature mast cell-like HMC-1 cells. Also, autophagy plays an important role in DENV infection and replication in these cells. Given the importance of ADE and FcR-bearing cells such as monocytes, macrophages and basophil/mast cells in dengue disease, the results provide insights into dengue pathogenesis and therapeutic means of control.

Original languageEnglish
Article number110655
JournalPLoS One
Volume9
Issue number10
DOIs
Publication statusPublished - Oct 16 2014
Externally publishedYes

Fingerprint

Dengue virus
Dengue Virus
basophils
Basophils
autophagy
Autophagy
Virus Diseases
mast cells
Viruses
Mast Cells
antibodies
Antibodies
infection
cells
dengue
Dengue
Antibody-Dependent Enhancement
Bearings (structural)
Macrophages
Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Autophagy facilitates antibody-enhanced dengue virus infection in human pre-basophil/mast cells. / Fang, Yi Ting; Wan, Shu Wen; Lu, Yi Tien; Yao, Ju Han; Lin, Chiou Feng; Hsu, Li Jin; Brown, Michael G.; Marshall, Jean S.; Anderson, Robert; Lin, Yee Shin.

In: PLoS One, Vol. 9, No. 10, 110655, 16.10.2014.

Research output: Contribution to journalArticle

Fang, YT, Wan, SW, Lu, YT, Yao, JH, Lin, CF, Hsu, LJ, Brown, MG, Marshall, JS, Anderson, R & Lin, YS 2014, 'Autophagy facilitates antibody-enhanced dengue virus infection in human pre-basophil/mast cells', PLoS One, vol. 9, no. 10, 110655. https://doi.org/10.1371/journal.pone.0110655
Fang, Yi Ting ; Wan, Shu Wen ; Lu, Yi Tien ; Yao, Ju Han ; Lin, Chiou Feng ; Hsu, Li Jin ; Brown, Michael G. ; Marshall, Jean S. ; Anderson, Robert ; Lin, Yee Shin. / Autophagy facilitates antibody-enhanced dengue virus infection in human pre-basophil/mast cells. In: PLoS One. 2014 ; Vol. 9, No. 10.
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AU - Lin, Chiou Feng

AU - Hsu, Li Jin

AU - Brown, Michael G.

AU - Marshall, Jean S.

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