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Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
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A functional interaction between GRP78 and Zika virus E protein.

Sarawut Khongwichit1, Wannapa Sornjai1, Kunlakanya Jitobaom1

  • 1Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, 25/25 Phuttamonthon 4 Road, Salaya, Nakhon Pathom, 73170, Thailand.

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The chaperone protein GRP78 interacts with the Zika virus (ZIKV) E protein, aiding viral entry and replication. Targeting this GRP78-ZIKV interaction may offer a new therapeutic strategy against Zika virus infection.

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Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Zika virus (ZIKV) poses a global health threat, linked to microcephaly in infants.
  • Mechanisms of ZIKV host cell interaction remain largely unknown.
  • The ZIKV E protein domain III is crucial for receptor binding.

Purpose of the Study:

  • To identify host proteins interacting with the ZIKV E protein.
  • To elucidate the role of GRP78 in ZIKV infection.
  • To explore GRP78 as a potential therapeutic target.

Main Methods:

  • Yeast-2-hybrid screening to identify ZIKV E interacting proteins.
  • Co-immunoprecipitation and immunofluorescence to confirm interactions and localization.
  • Antibody inhibition and siRNA to assess GRP78's role in viral entry and replication.
  • Analysis of unfolded protein response (UPR) markers.

Main Results:

  • GRP78 was identified as a ZIKV E interacting protein.
  • GRP78 facilitates ZIKV binding, internalization, and replication.
  • Antibodies against GRP78 and GRP78 knockdown inhibited ZIKV infection.
  • ZIKV infection upregulated GRP78 and activated the UPR.

Conclusions:

  • The interaction between GRP78 and ZIKV E protein is vital for ZIKV infection.
  • GRP78 plays a significant role in mediating ZIKV entry and replication.
  • Targeting the GRP78-ZIKV interaction presents a potential therapeutic avenue.