Challenging the Conventional Interpretation of HCMV Seronegativity

Abstract

The majority of adults in the world (around 83%) carry antibodies reactive with HCMV and are thought to retain inactive or latent infections lifelong. The virus is transmitted via saliva, so infection events are likely to be common. Indeed, it is hard to imagine a life without exposure to HCMV. From 45 seronegative individuals (13 renal transplant recipients, 32 healthy adults), we present seven cases who had detectable HCMV DNA in their blood and/or saliva, or a CMV-encoded homologue of IL-10 (vIL-10) in their plasma. One case displayed NK cells characteristic of CMV infection before her HCMV DNA became undetectable. In other cases, the infection may persist with seroconversion blocked by vIL-10. Future research should seek mechanisms that can prevent an individual from seroconverting despite a persistent HCMV infection, as HCMV vaccines may not work well in such people.

Sequencing of the Viral UL111a Gene Directly from Clinical Specimens Reveals Variants of HCMV-Encoded IL-10 That Are Associated with Altered Immune Responses to HCMV

“…Here, we used a nested PCR, followed by a deep sequencing approach, on HCMV directly from clinical samples from PWH, RTR, healthy controls, and neonates, to study variations in UL111a. Three seronegative individuals (1 RTR and 2 controls) yielded UL111a sequences, but these were not distinguishable as a group [31]. Multi-variant infections were common (55/59 samples).…”