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Male germ cells support long-term propagation of Zika virus

Christopher L Robinson1, Angie C N Chong1, Alison W Ashbrook2

  • 1Department of Surgery, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA.

Nature Communications
|May 31, 2018
PubMed

Insights

Zika virus (ZIKV) can infect and replicate in testicular germ cells (GCs), potentially leading to sexual transmission. Berberine chloride shows promise in inhibiting ZIKV in testes.

Area of Science:

  • Virology
  • Reproductive Biology
  • Immunology

Background:

  • Zika virus (ZIKV) sexual transmission is a significant public health concern.
  • Evidence suggests ZIKV can persist in semen, implicating testicular cells in viral propagation.
  • The specific testicular cell types susceptible to ZIKV and their role in viral shedding remain unclear.

Purpose of the Study:

  • To identify testicular cells susceptible to ZIKV infection.
  • To investigate the mechanisms of ZIKV replication in testicular cells.
  • To identify potential therapeutic agents against ZIKV testicular infection and sexual transmission.

Main Methods:

  • Infection of primary murine and human testicular cells with ZIKV, dengue virus, and yellow fever virus.
  • Assessment of viral replication and infectious virus production.
  • Analysis of interferon-stimulated gene Ifi44l expression in infected cells.
  • Evaluation of berberine chloride as an antiviral agent in murine and human testicular explants.

Main Results:

  • Germ cells (GCs) were identified as the most susceptible testicular cells to ZIKV infection.
  • ZIKV-infected GCs produced high levels of infectious virus, unlike cells infected with related flaviviruses.
  • ZIKV infection in GCs led to decreased expression of Ifi44l, an interferon-stimulated gene.
  • Overexpression of Ifi44l reduced ZIKV production in GCs.
  • Primary human GCs were also permissive to ZIKV infection and production.
  • Berberine chloride demonstrated potent inhibition of ZIKV infection in both murine and human testes.

Conclusions:

  • Testicular germ cells are a key cellular target for ZIKV replication and may serve as a reservoir for viral propagation.
  • Downregulation of Ifi44l in GCs contributes to efficient ZIKV replication.
  • Berberine chloride is a promising candidate drug for preventing ZIKV testicular infection and subsequent sexual transmission.

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