Animal models of human cytomegalovirus congenital infection

Abstract

Human cytomegalovirus (HCMV) infection is highly species-specific, which means that it is unable to productively infect laboratory animals. Despite this caveat, studies of animal CMV counterparts in their natural hosts have revealed significant correlations with observed neuropathological effects of congenital HCMV infection and have improved our understanding of host responses to vaccination. The biological relatedness between human and animal CMVs has been confirmed by phylogenetic analyses; the conservation of ‘core' genes that are essential for virus replication as well as genes that contribute similar mechanisms for virus persistence in their respective host species. The common animal models of HCMV congenital infection include Rhesus CMV (RhCMV), guinea-pig CMV (GPCMV) and mouse CMV (MCMV). Whilst animal models of CMV do not fully recapitulate HCMV infection, they each offer specific advantages in understanding HCMV congenital/perinatal infection (summarised in Table 1).

Human cytomegalovirus (CMV) dysregulates neurodevelopmental pathways in cerebral organoids

“…Two-dimensional cell monocultures used in assessment of infection effects do not take into account the specific gene regulation patterns of different cell populations within the human brain 24 – 26 . Animal models, although consisting of multiple cell and organ types, are not able to accurately represent human CMV infection due to the species-specific nature of the virus 27 . Congruent with previous studies of Lancaster et al, the organoids generated here developed complex structures, different cerebral regions, and different cell types, displaying the three-dimensional organisation which resembled in vivo brain development.…”