A COMPARATIVE ANALYSIS OF AGES AND INFECTION ROUTES IN CMV MOUSE MODELS

Abstract

Cytomegalovirus (CMV) is a ubiquitous human virus that is notable due to its prevalence world-wide and its ability to persist throughout its host’s lifetime. Murine cytomegalovirus (MCMV) is commonly utilized to model human cytomegalovirus (HCMV) in order to investigate the host:virus interaction, including virus pathogenesis, immune evasion, immunity, and this virus’s impact on host health. In order to examine the impact that route and age have on modeling of the HCMV infection in mice, we performed a comparative analysis of prepubescent (4-week-old) and young adult (12-week-old) mice infected through two common experimental modes of infection (intraperitoneal or intranasal). Although we found that both routes of infection resulted in similar early viral loads, we did observe differences in the deployment of the immune response. Notably, the 4-week-old mice infected intraperitoneally showed the strongest NK cell response when measuring the overall NK cell population as well as the population of NK cells that expressed Ly49H (a MCMV-specific receptor). Intraperitoneally infected mice, especially the 12-week-old cohort, also exhibited a strong adaptive immune response as demonstrated by the accumulation of a larger concentration of anti-MCMV IgG and a greater expansion of CD8+ T cells during both the acute and latent phases. The differences in immune responses as a function of age and infection routes suggest that these parameters are significant and should be considered when modeling HCMV using the MCMV model system.