Erp57 facilitates ZIKV-induced DNA damage via NS2B/NS3 complex formation

Area of Science:

• Neuroscience
• Virology
• Molecular Biology

Background:

• Zika virus (ZIKV) infection in pregnant women is linked to severe brain damage in newborns, including microcephaly.
• The precise mechanisms underlying ZIKV-induced neurodevelopmental defects remain poorly understood.

Purpose of the Study:

• To investigate the role of ERp57, a protein disulfide isomerase (PDI) family member, in ZIKV infection and pathogenesis.
• To elucidate the molecular mechanisms by which ZIKV induces DNA damage in nerve cells.

Main Methods:

• Utilized ERp57 knockout nerve cells to assess ZIKV production and DNA damage.
• Investigated the role of ERp57 in viral protein complex formation (NS2B/NS3).
• Employed ERp57 inhibitor LOC14 to evaluate its effect on ZIKV infection and DNA damage.

Main Results:

• ERp57 depletion limited ZIKV production in nerve cells.
• ERp57 knockout suppressed ZIKV-induced reactive oxygen species (ROS)-mediated DNA damage and reduced apoptosis.
• ZIKV-induced DNA damage was dependent on an ERp57-bridged complex of viral proteins NS2B/NS3.
• The ERp57 inhibitor LOC14 restricted ZIKV infection and associated DNA damage.

Conclusions:

• ERp57 plays a critical role in both ZIKV propagation and the induction of host DNA damage.
• Targeting ERp57 presents a potential therapeutic strategy to combat ZIKV infection and its neurological consequences.