Sensitivity of Human Mastadenovirus, the Causal Agent of Pharyngoconjunctival Fever, Epidemic Keratoconjunctivitis, and Hemorrhagic Cystitis in Immunocompromised Individuals, to Brincidofovir

Microbiol Spectr. 2022 Feb 23;10(1):e0156921. doi: 10.1128/spectrum.01569-21. Epub 2022 Feb 16.

Abstract

Human mastadenovirus (HAdV), a linear double-stranded DNA (dsDNA) virus, is the causal agent of several diseases, including pharyngoconjunctival fever, epidemic keratoconjunctivitis, and hemorrhagic cystitis, in immunocompromised individuals. There are more than 100 reported types of adenoviruses, but the pathogenicity of many HAdVs remains unknown. Brincidofovir (BCV) is a hexadecyloxypropyl lipid conjugate of cidofovir (CDV) that is active against dsDNA viruses. Clinical effectiveness of BCV against certain HAdV species has been reported; however, its activity against novel HAdV types remains unknown. We investigated the half-maximal inhibitory concentration (IC50) values of BCV for novel HAdV types and found that the epidemic keratoconjunctivitis-associated HAdV-D54 prevalent in the Asian region was the most susceptible. The mean overall IC50 value of BCV was lower than that of CDV, indicating that BCV is effective against HAdVs, including the novel types. IMPORTANCE We investigated the IC50 values of BCV for novel HAdV types and found that the epidemic keratoconjunctivitis-associated HAdV-D54 prevalent in the Asian region was the most susceptible. In addition, the mean overall IC50 value of BCV was lower than that of CDV, indicating that BCV is effective against HAdVs.

Keywords: brincidofovir; half-maximal inhibitory concentration; human mastadenovirus; novel type.

MeSH terms

  • Adenoviridae Infections / immunology
  • Adenoviridae Infections / virology*
  • Adenovirus Infections, Human / immunology
  • Adenovirus Infections, Human / virology*
  • Cystitis
  • Cytosine / analogs & derivatives*
  • Cytosine / pharmacology
  • Humans
  • Immunocompromised Host
  • Keratoconjunctivitis / immunology
  • Keratoconjunctivitis / virology*
  • Mastadenovirus / classification
  • Mastadenovirus / drug effects*
  • Mastadenovirus / genetics
  • Mastadenovirus / physiology
  • Organophosphonates / pharmacology*

Substances

  • Organophosphonates
  • brincidofovir
  • Cytosine