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Review
. 2020 Mar 5;221(Suppl 1):S60-S73.
doi: 10.1093/infdis/jiz484.

Animal Models of Congenital Cytomegalovirus Transmission: Implications for Vaccine Development

Hunter K Roark  1 , Jennifer A Jenks  1 , Sallie R Permar  1 , Mark R Schleiss  2
Affiliations
Review

Animal Models of Congenital Cytomegalovirus Transmission: Implications for Vaccine Development

Hunter K Roark et al. J Infect Dis. .

Abstract

Although cytomegaloviruses (CMVs) are species-specific, the study of nonhuman CMVs in animal models can help to inform and direct research aimed at developing a human CMV (HCMV) vaccine. Because the driving force behind the development of HCMV vaccines is to prevent congenital infection, the animal model in question must be one in which vertical transmission of virus occurs to the fetus. Fortunately, two such animal models-the rhesus macaque CMV and guinea pig CMV-are characterized by congenital infection. Hence, each model can be evaluated in "proof-of-concept" studies of preconception vaccination aimed at blocking transplacental transmission. This review focuses on similarities and differences in the respective model systems, and it discusses key insights from each model germane to the study of HCMV vaccines.

Keywords: Congenital cytomegalovirus; cytomegalovirus glycoproteins; cytomegalovirus vaccines; guinea pig cytomegalovirus; rhesus macaque cytomegalovirus.

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Figures

Figure 1.
Figure 1.
Comparison of guinea pig cytomegalovirus (GPCMV), rhesus macaque CMV (RhCMV), and human CMV (HCMV) genomes. Side-by-side comparison of collinearity of respective CMV genomes and selected open reading frames (ORFs) in ~20-kilobase segment adjacent to major immediate early (MIE) region. (Top Panel) The GPCMV (salivary gland isolate, strain 22122; GenBank accession number NC_020231); (middle panel) RhCMV (strain 180.92, GenBank accession number DQ120516); (bottom panel) HCMV (strain TBE/40, GenBank accession number EF999921). Conserved regions circled in red represent highly conserved MIE transcripts for each virus. The ORFs circled in blue represent smaller subunits of conserved CMV pentamer. Three smaller proteins complex with gH (gpUL75) and gL (gpUL115); the nomenclature for these smaller subunits varies among the 3 CMV species as reviewed in the text. Other adjacent ORFs in this genome region have been identified as playing roles in viral pathogenesis as discussed in the text.
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