Inhibition of Human Cytomegalovirus Particle Maturation by Activation of Liver X Receptor

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of liver X receptor (LXR) can significantly inhibit the replication of HCMV and weaken the virulence of progeny virus (unpublished data).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.

LXR-inducible host E3 ligase IDOL targets a human cytomegalovirus reactivation determinant

“…Activation of LXR in human foreskin fibroblasts with GW3965 prior to HCMV infection was reportedly shown to depresses expression levels of viral proteins, such as IE2, pp28, pp65 and gB (76). GW3965 treatment is also reported to induce IFN-γ (77), a cytokine which directly inhibits IE1/2 mRNA expression (78).…”

Resistance profile ofEscherichia coliisolated from stool, feed, and compost sources to antibiotics in Sukabumi

“…On the other hand, gentamicin is an aminoglycoside-type antibiotic that is commonly used in the veterinary practices, which exhibits efficacy against both gram-positive and gram-negative bacteria [25]. Studies Liu et al (2022) [26] and Sabir et al (2014) [27] seasons. Bacteria resistant to gentamicin from livestock environments raises concerns, as it can potentially enter the meat supply chain for human consumption [25].…”

Cholesterol metabolism in rheumatic diseases

“…В частности, Х-рецепторы печени (liver X receptor, LXR) являются ключевыми транскрипционными факторами в регуляции метаболизма липидов и гомеостаза холестерина. Помимо этого они влияют на врожденный и адаптивный иммунитет, включая ответы на воспалительные стимулы, пролиферацию и дифференцировку, миграцию и апоптоз [22]. Активация LXR приводит к индукции экспрессии генов, кодирующих белки, участвующие в процессах оттока холестерина, в частности АТФсвязывающего кассетного транспортера A1 (ATP binding cassette subfamily a member 1, ABCA1) и G1 (ATP-binding cassette sub-family G member 1, ABCG1), аполипопротеина E (apolipoprotein E, ApoE).…”