Viral interference during coinfection and sequential infection of enterovirus A71 and coxsackievirus A16

Hooi Yee Chang1, Kien Chai Ong2, Kartini Jasni3

  • 1Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Malaysia.

Virology
|June 26, 2025
PubMed

Insights

Viral interference between enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) was experimentally demonstrated. Prior EV-A71 infection protected mice against subsequent CVA16 infection, suggesting potential for combined vaccines.

Area of Science:

  • Virology
  • Immunology
  • Infectious Diseases

Background:

  • Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by enteroviruses, notably enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16).
  • These viruses frequently co-circulate, raising the possibility of viral interference impacting disease transmission, severity, and vaccine efficacy.
  • Epidemiological data suggest potential interference between EV-A71 and CVA16, but experimental evidence is limited.

Purpose of the Study:

  • To experimentally investigate viral interference between EV-A71 and CVA16 in cell culture and a mouse model.
  • To assess the impact of coinfection and sequential infection on viral replication, mortality, and immune responses.
  • To explore the potential for developing combined EV-A71 and CVA16 vaccines.

Main Methods:

  • Coinfection and sequential infection experiments were conducted using rhabdomyosarcoma (RD) cells and BALB/c mice.
  • Mice were infected with mouse-adapted EV-A71 (MP4) and/or CVA16, either simultaneously or sequentially.
  • Outcomes measured included viral replication, mortality rates, viral RNA levels in tissues, histopathological changes, and innate immune gene/cytokine expression.

Main Results:

  • In RD cells, prior EV-A71 infection inhibited CVA16 replication.
  • In mice, coinfection reduced mortality, and prior EV-A71 infection significantly reduced mortality from subsequent EV-A71 or CVA16 infection compared to single infections.
  • Coinfection altered innate immune responses in mice, while prior EV-A71 infection suppressed CVA16 replication and modulated specific immune gene expressions.

Conclusions:

  • Experimental evidence confirms viral interference between EV-A71 and CVA16 during coinfection and sequential infection.
  • Prior EV-A71 infection confers protection against subsequent CVA16 infection in a mouse model.
  • A coadministered or sequential EV-A71 and CVA16 vaccine strategy could potentially offer broad innate immune protection against HFMD.

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