Reddehase, Matthias J.; Balthesen, Monika; Rapp, Maria; Jonjic, Stipan; Pavic, Ivica; Koszinowski, Ulrich H.
The Conditions of Primary Infection Define the Load of Latent Viral Genome in Organs and the Risk of Recurrent Cytomegalovirus Disease.
In: The journal of experimental medicine, Vol. 179: pp. 185-193
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.