The Conditions of Primary Infection Define the Load of Latent Viral Genome in Organs and the Risk of Recurrent Cytomegalovirus Disease

Recurrence of cytomegalovirus (CMV) from latency is a frequent
cause of disease in immunocompromised patients. To date, there is
no explanation for the diversity in the clinical manifestations.
Primary infection can occur perinatally or later in life, and
inevitably results in latent infection. Seropositivity for
antibodies against CMV is indicative of latent infection, but is
insufficient as a predictor for the risk of recurrence. As a model
for this important medical problem, we compared the risks of murine
CMV recurrence from latency established after neonatal primary
infection and after infection at adult age. The risk of CMV
recurrence was high only after neonatal infection. The copy number
of latent viral genome in tissues was identified as the key
parameter that determines the overall and organ-specific risks of
recurrence. Latent CMV burden and risk of recurrence were related
to the extent of virus multiplication during primary infection. The
presence of latent CMV in multiple organs provides the molecular
basis for stochastic events of recurrence in single organs or in
any combination thereof. These findings are discussed as a concept
of multifocal CMV latency and recurrence. It provides a rationale
for the diversity in the clinical outcome of CMV disease.