Cytomegalovirus virions shed in urine have a reversible block to epithelial cell entry and are highly resistant to antibody neutralization

Xiaohong Cui, Stuart P. Adler, Mark R. Schleiss, Ravit Boger, Gail J. Demmler Harrison, Michael A. McVoy

Research output: Contribution to journalArticle

Abstract

Cytomegalovirus (CMV) causes sensorineural hearing loss and developmental disabilities in newborns when infections are acquired in utero. Pregnant women may acquire CMV from oral exposure to CMV in urine or saliva from young children. Neutralizing antibodies in maternal saliva have the potential to prevent maternal infection and, in turn, fetal infection. As CMV uses different viral glycoprotein complexes to enter different cell types, the first cells to be infected in the oral cavity could determine the type of antibodies needed to disrupt oral transmission. Antibodies targeting the pentameric complex (PC) should block CMV entry into epithelial cells but not into fibroblasts or Langerhans cells (which do not require the PC for entry), while antibodies targeting glycoprotein complexes gB or gH/gL would be needed to block entry into fibroblasts, Langerhans cells, or other cell types. To assess the potential for antibodies to disrupt oral acquisition, CMV from culturepositive urine samples (uCMV) was used to study cell tropisms and sensitivity to antibody neutralization. uCMV entered epithelial cells poorly compared with the entry into fibroblasts. CMV-hyperimmune globulin or monoclonal antibodies targeting gB, gH/gL, or the PC were incapable of blocking the entry of uCMV into either fibroblasts or epithelial cells. Both phenotypes were lost after one passage in cultured fibroblasts, suggestive of a nongenetic mechanism. These results suggest that uCMV virions have a reversible block to epithelial cell entry. Antibodies may be ineffective in preventing maternal oral CMV acquisition but may limit viral spread in blood or tissues, thereby reducing or preventing fetal infection and disease.

Original languageEnglish (US)
Article numbere00024-17
JournalClinical and Vaccine Immunology
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Cytomegalovirus
Virion
Fibroblasts
Epithelial Cells
Urine
Antibodies
Langerhans Cells
Glycoproteins
Mothers
Infection
Saliva
Globulins
Audition
Fetal Diseases
Neutralizing Antibodies
Developmental Disabilities
Tropism
Sensorineural Hearing Loss
Blood
Monoclonal Antibodies

Keywords

  • Congenital infection
  • Cytomegalovirus
  • Neutralizing antibodies
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Cytomegalovirus virions shed in urine have a reversible block to epithelial cell entry and are highly resistant to antibody neutralization. / Cui, Xiaohong; Adler, Stuart P.; Schleiss, Mark R.; Boger, Ravit; Demmler Harrison, Gail J.; McVoy, Michael A.

In: Clinical and Vaccine Immunology, Vol. 24, No. 6, e00024-17, 01.06.2017.

Research output: Contribution to journalArticle

Cui, Xiaohong ; Adler, Stuart P. ; Schleiss, Mark R. ; Boger, Ravit ; Demmler Harrison, Gail J. ; McVoy, Michael A. / Cytomegalovirus virions shed in urine have a reversible block to epithelial cell entry and are highly resistant to antibody neutralization. In: Clinical and Vaccine Immunology. 2017 ; Vol. 24, No. 6.
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