Zika virus targets the human thymic epithelium

Area of Science:

• Virology
• Immunology
• Developmental Biology

Background:

• The thymus is crucial for T-cell development.
• Previous studies identified RNA virus infections (HIV, HTLV-1) in the thymus.
• The potential for Zika virus (ZIKV) infection of the thymus remained unexplored.

Purpose of the Study:

• To investigate whether the Zika virus (ZIKV) infects human thymic epithelial cells (TEC).
• To characterize the effects of ZIKV infection on TEC function and gene expression.
• To examine ZIKV's impact on T-cell interactions within the thymus.

Main Methods:

• In vitro infection of human TEC with ZIKV.
• Analysis of TEC proliferation, cell death, and keratinization.
• RNA sequencing to assess coding and non-coding gene expression changes.
• In vivo examination of thymuses from congenitally ZIKV-infected infants.

Main Results:

• ZIKV successfully infected human TEC in vitro and in vivo.
• ZIKV infection altered TEC keratinization, reduced proliferation, and increased cell death.
• Significant modulation of coding and non-coding RNAs, including genes for cell adhesion and migration.
• Increased lymphoblastic T-cell attachment to and virus transfer from infected TEC.
• Thymic alterations and presence of ZIKV envelope protein in TEC of congenitally infected infants.

Conclusions:

• The human thymus, specifically thymic epithelium, is a target for ZIKV.
• ZIKV infection alters TEC properties and gene expression, potentially affecting thymocyte development.
• Findings highlight the thymus as a site of ZIKV replication and potential T-cell dysfunction.