Human Cytomegalovirus Primary Infection and Reactivation: Insights From Virion-Carried Molecules

Abstract

Human cytomegalovirus (HCMV), a ubiquitous beta-herpesvirus, is able to establish lifelong latency after initial infection. Periodical reactivation occurs after immunosuppression, remaining a major cause of death in immunocompromised patients. HCMV has to reach a structural and functional balance with the host at its earliest entry. Virion-carried mediators are considered to play pivotal roles in viral adaptation into a new cellular environment upon entry. Additionally, one clear difference between primary infection and reactivation is the idea that virion-packaged factors are already formed such that those molecules can be used swiftly by the virus. In contrast, virion-carried mediators have to be transcribed and translated; thus, they are not readily available during reactivation. Hence, understanding virion-carried molecules helps to elucidate HCMV reactivation. In this article, the impact of virion-packaged molecules on viral structure, biological behavior, and viral life cycle will be reviewed.

Keywords: HCMV; envelope; primary infection; reactivation; tegument; virion-carried molecules.

FIGURE 1

Roles of pp71 in the lytic and latent phase. The left panel shows lytic gene expression. Nuclear pp71 is capable of promoting pUL35 to recruit PML, an ND10 component that has impacts on correct localization of Daxx and Sp100. pp71 interacts with Daxx and induces Daxx for degradation in a proteasome-dependent manner. pp71 transactivates IE gene expression, and IE products disrupt ND10. pp71 also has abilities to induce Rb degradation, a process that contributes to relieve Rb-mediated cell cycle block. The right panel shows the latent state and reactivation. pp71 is retained in the cytoplasm or endosome rather than the nucleus. ND10 components represent an intrinsic defense mechanism. Daxx, PML, and bound transcription factors recruit histone deacetylases, resulting in viral gene silencing. LUNA-mediated reactivation is shown in a black circle. LUNA contains isopeptidase activity that deSUMOylates PML and disrupts PML-induced recruitment of Daxx and Sp100. Therefore, LUNA promotes reactivation.