Human Cytomegalovirus (HCMV) transcripts (including UL21.5 mRNA)
have been found to be packaged in virions and their detection in plasma
may indicate the presence of infectious viral particles. Objective of
this study was to verify whether UL21.5 mRNA detected in the plasma was
indeed encapsulated in viral particles, representing an indirect marker
of active replication. To distinguish between virion-packaged and
free-floating RNA, plasma samples from 22 immunocompromised patients
were tested before and after ribonuclease (RNAse) digestion. UL21.5 mRNA
was detected 1-2 weeks prior to preemptive therapy administration in 20
episodes (from 18 patients) of clinically significant DNAemia, while it
was undetectable in three of the four patients with transient,
self-resolving DNAemia. After RNAse digestion, UL21.5 mRNA was still
detectable, with a median reduction of 0.1 (IQ range 0-0.3)
Log10. Concentrations of UL21.5 mRNA in plasma
correlated significantly with HCMV DNA in whole blood or plasma
(R=0.67), and 75% of samples positive for UL21.5 mRNA had HCMV DNA
concentrations above 104 copies/ml blood or
103 copies/ml plasma. Moreover, UL21.5 mRNA was
positive in patients who developed HCMV infection resistant to
letermovir or maribavir, whereas it was undetectable in plasma of
patients with transient self-resolving DNAemia blips during letermovir
prophylaxis (not associated with drug-resistance). HCMV UL21.5 mRNA in
plasma is virion-associated and represents a marker for productive HCMV
infection. The determination of UL21.5 mRNA could improve current
strategies for the management of HCMV infection in immunocompromised
patients.
Key words: human cytomegalovirus; mRNA; virion; transplant
recipients; immunocompromised patients.