Pathologic and immunologic characteristics of coxsackievirus A16 infection in rhesus macaques

Virology. 2017 Jan:500:198-208. doi: 10.1016/j.virol.2016.10.031. Epub 2016 Nov 6.

Abstract

Coxsackievirus A16 (CV-A16) causes human hand, foot and mouth disease, but its pathogenesis is unclear. In rhesus macaques, CV-A16 infection causes characteristic vesicles in the oral mucosa and limbs as well as viremia and positive viral loads in the tissues, suggesting that these animals reflect the pathologic process of the infection. An immunologic analysis indicated a defective immune response, which included undetectable neutralizing antibodies and IFN-γ-specific memory T-cells in macaques infected with CV-A16. Furthermore, existing neutralizing antibodies in macaques immunized with the inactivated vaccine were surprisingly unable to protect against a viral challenge despite the presence of a positive T-cell memory response against viral antigens. The virus was capable of infecting pre-conventional dendritic cells and replicating within them, which may correlate with the immunological characteristics observed in the animals.

Keywords: Coxsackievirus A16 (CV-A16); Dendritic cell (DC); Inactivated vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / virology
  • Disease Models, Animal
  • Enterovirus A, Human / genetics
  • Enterovirus A, Human / pathogenicity
  • Enterovirus A, Human / physiology*
  • Hand, Foot and Mouth Disease / immunology*
  • Hand, Foot and Mouth Disease / pathology
  • Hand, Foot and Mouth Disease / prevention & control
  • Hand, Foot and Mouth Disease / virology
  • Humans
  • Interferon-gamma / immunology
  • Macaca mulatta
  • Neutralization Tests
  • T-Lymphocytes / immunology
  • Viral Vaccines / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Vaccines
  • Interferon-gamma