Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission

Kristy M. Bialas, Takayuki Tanaka, Dollnovan Tran, Valerie Varner, Eduardo Cisneros De La Rosa, Flavia Chiuppesi, Felix Wussow, Lisa Kattenhorn, Sheila Macri, Erika L. Kunz, Judy A. Estroff, Jennifer Kirchherr, Yujuan Yue, Qihua Fan, Michael Lauck, David H. O'Connor, Allison H S Hall, Alvarez Xavier, Don J. Diamond, Peter A BarryAmitinder Kaur, Sallie R. Permar

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Elucidation of maternal immune correlates of protection against congenital cytomegalovirus (CMV) is necessary to inform future vaccine design. Here, we present a novel rhesus macaque model of placental rhesus CMV (rhCMV) transmission and use it to dissect determinants of protection against congenital transmission following primary maternal rhCMV infection. In this model, asymptomatic intrauterine infection was observed following i.v. rhCMV inoculation during the early second trimester in two of three rhCMV-seronegative pregnant females. In contrast, fetal loss or infant CMV-associated sequelae occurred in four rhCMV-seronegative pregnant macaques that were CD4+ T-cell depleted at the time of inoculation. Animals that received the CD4+ T-cell-depleting antibody also exhibited higher plasma and amniotic fluid viral loads, dampened virus-specific CD8+ T-cell responses, and delayed production of autologous neutralizing antibodies compared with immunocompetent monkeys. Thus, maternal CD4+ T-cell immunity during primary rhCMV infection is important for controlling maternal viremia and inducing protective immune responses that prevent severe CMV-associated fetal disease.

Original languageEnglish (US)
Pages (from-to)13645-13650
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number44
DOIs
StatePublished - Nov 3 2015

Keywords

  • Congenital cytomegalovirus
  • Neutralizing antibody
  • Rhesus CMV
  • Rhesus model
  • T-cell immunity

ASJC Scopus subject areas

  • General

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