Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and low pH

Mirjana Persaud, Alicia Martinez-Lopez, Cindy Buffone, Steven A. Porcelli, Felipe Diaz-Griffero

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The recent Zika virus (ZIKV) outbreak in Brazil has suggested associations of this virus infection with neurological disorders, including microcephaly in newborn infants and Guillian-Barré syndrome in adults. Previous reports have shown that AXL, a transmembrane receptor tyrosine kinase protein, is essential for ZIKV infection of mammalian cells, but this remains controversial. Here, we have assessed the involvement of AXL in the ability of ZIKV to infect mammalian cells, and also the requirement for endocytosis and acidic pH. We demonstrated that AXL is essential for ZIKV infection of human fibroblast cell line HT1080 as the targeted deletion of the gene for AXL in HT1080 cells made them no longer susceptible to ZIKV infection. Our results also showed that infection was prevented by lysosomotropic agents such as ammonium chloride, chloroquine and bafilomycin A1, which neutralize the normally acidic pH of endosomal compartments. Infection by ZIKV was also blocked by chlorpromazine, indicating a requirement for clathrin-mediated endocytosis. Taken together, our findings suggest that AXL most likely serves as an attachment factor for ZIKV on the cell surface, and that productive infection requires endocytosis and delivery of the virus to acidified intracellular compartments.

Original languageEnglish (US)
Pages (from-to)301-312
Number of pages12
JournalVirology
Volume518
DOIs
StatePublished - May 1 2018

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Endocytosis
Proteins
Ammonium Chloride
Microcephaly
Clathrin
Chlorpromazine
Gene Deletion
Chloroquine
Receptor Protein-Tyrosine Kinases
Virus Diseases
Infection
Nervous System Diseases
Disease Outbreaks
Brazil
Fibroblasts
Newborn Infant
Viruses
Cell Line
Zika Virus Infection
Zika Virus

Keywords

  • Clathrin
  • Endocytosis
  • Entry
  • Low-pH
  • ZIKA

ASJC Scopus subject areas

  • Virology

Cite this

Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and low pH. / Persaud, Mirjana; Martinez-Lopez, Alicia; Buffone, Cindy; Porcelli, Steven A.; Diaz-Griffero, Felipe.

In: Virology, Vol. 518, 01.05.2018, p. 301-312.

Research output: Contribution to journalArticle

Persaud, Mirjana ; Martinez-Lopez, Alicia ; Buffone, Cindy ; Porcelli, Steven A. ; Diaz-Griffero, Felipe. / Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and low pH. In: Virology. 2018 ; Vol. 518. pp. 301-312.
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