Abstract
Human cytomegalovirus (HCMV), a herpesvirus family member, is a large, complex enveloped virus. The activation of liver X receptor (LXR) can significantly inhibit the replication of HCMV and weaken the virulence of progeny virus (unpublished data). Our results showed activated LXR affected some important viral protein expression and reduced cholesterol content in HCMV infected cells and virus particles. To further clarify the influence of activated LXR on HCMV replication, HCMV assembly and maturation processes were studied by transmission electron microscopy (TEM) in HCMV infected foreskin fibroblasts treated with LXR agonist GW3965. Results showed that activated LXR could reduce the envelope integrity of maturating virions. The functional stage of activated LXR on viral envelope integrity was mainly at virus assembly compartment (VAC) mediated envelopment but not structurally complete virus nucleocapsid formation and the egress of nucleocapsid from the nucleus to the cytoplasm mediated by nuclear egress complex. Reduced cholesterol synthesis and viral protein expression might interfere with the VAC-mediated envelopment. The nucleocapsid and tegument proteins enter the VAC area for the secondary envelope, which was interfered with and resulted in the defective particle, thereby affecting the amount and infectivity of the mature virus. The results indicate that inhibition of HCMV maturation is one mechanism of activated LXR inhibiting virus replication in infected cells.
Highlights
Human cytomegalovirus (HCMV) is a large, complex enveloped virus that belongs to the herpesvirus family (Mettenleiter et al, 2009)
To clarify whether the activated liver X receptor (LXR) affects the expression of important proteins, LXR-α, IE, gB, pp65, pp28, and pp52 in infected cells and purified progeny virions were detected by Western blot
Through comparative analysis of the experimental results, we found that the expression level of pp52, which is the accessory subunit of DNA polymerase, was not almost changed in cells and purified progeny virions from the cells whatever treatments with or without GW3965
Summary
Human cytomegalovirus (HCMV) is a large, complex enveloped virus that belongs to the herpesvirus family (Mettenleiter et al, 2009). HCMV infection causes severe diseases in immunocompromised individuals such as AIDS patients and organ transplant recipients and is the most common and harmful pathogen causing congenital infection and birth defects (Landázuri et al, 2021). Our study (unpublished data) has shown that HCMV growth was remarkably inhibited by the activation of liver X receptor (LXR). Virus particles undergo a series of complex processes during packaging and maturation. It was worth investigating how activated LXR affected the virus titers and infectivity of progeny virus
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