Animal models of congenital cytomegalovirus infection: An overview of progress in the characterization of guinea pig cytomegalovirus (GPCMV)

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Abstract

Background: The strict species-specificity of cytomegalovirus (CMV) precludes preclinical evaluation of human CMV (HCMV) vaccines in animal models and necessitates the study of nonhuman CMVs. Among the CMVs of small mammals, the guinea pig cytomegalovirus (GPCMV) has unique advantages, due to its ability to cross the placenta, causing infection in utero. Objective and study designs: Progress in GPCMV studies has been hampered by a lack of detailed molecular characterization of the viral genome. Therefore, recent efforts have been undertaken to characterize the GPCMV genome, and apply this information to in vivo subunit vaccine studies. Results: Progress in the sequencing of the GPCMV genome has revealed the presence of both highly conserved as well as novel open reading frames (ORFs). Cloning of GPCMV vaccine candidates, such as the glycoprotein B (gB) and UL83 proteins, has facilitated subunit vaccine evaluation. Protein vaccines and DNA vaccines have shown evidence of protection in pregnancy/challenge experiments. In addition, the GPCMV genome has proved amenable to cloning as a bacterial artificial chromosome (BAC) in Escherichia coli, and BAC-derived recombinants retain the ability to replicate in vivo. Conclusions: Progress has been made in molecular characterization of GPCMV. Insights from these studies should prove germane to the understanding of the correlates of protective immunity for the fetus in vaccine studies, and should assist in prioritization of vaccine strategies in HCMV vaccine trials.

Original languageEnglish (US)
Pages (from-to)37-49
Number of pages13
JournalJournal of Clinical Virology
Volume25
Issue numberSUPPL. 2
DOIs
StatePublished - Aug 2002

Bibliographical note

Funding Information:
I acknowledge the contributions of many skilled technicians, in particular Debbie Fox and Nancy Jensen, to this work. I gratefully acknowledge the effort of my principle collaborators in animal studies, Dr Nigel Bourne, and molecular studies, Dr Alistair McGregor. I thank Fernando Bravo, Mike McVoy, Jeff Vieira, Martin Messerle and Ulrich Koszinowski for helpful discussions, plasmids, and protocols. I acknowledge the advice and assistance of the Director of the Division of Infectious Diseases at Children's Hospital, Cincinnati, David Bernstein. Finally, I am indebted to Collett Mack Schleiss for helpful discussions and support. These studies were supported by NIH HD38416-01 and AI65289 and March of Dimes Basiv Research Grants 6-FY98/99-0416 and FY01-226.

Keywords

  • CMV vaccines
  • Cytomegalovirus (CMV)
  • Guinea pig

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