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Inhibition of human cytomegalovirus maturation by brefeldin A
M Eggers1, E Bogner, B Agricola
1Institut für Virologie, Philipps-Universität, Marburg, Germany.
Abstract:
Brefeldin A (BFA) was found to interfere with specific events of human cytomegalovirus (HCMV) maturation in human fibroblasts. Ultrastructural as well as biochemical studies suggested that short-term exposure of infected cultures to BFA during the late infectious cycle primarily prevented Golgi-dependent processes, e.g. envelopment of naked cytoplasmic nucleocapsids in the trans-Golgi network (TGN) and normal processing of glycoprotein B. In contrast, the nuclear phase of viral morphogenesis, e.g. transport budding at the nuclear envelope, was not impaired. These observations were compatible with the interpretation that HCMV morphogenesis may involve sequential budding events at the nuclear envelope and at cisternae of the TGN. BFA treatment during the early infectious cycle efficiently inhibited HCMV-DNA synthesis and thus late viral functions, preventing production of viral progeny. Cytotoxicity was excluded as a cause for these findings.
Insights
Brefeldin A (BFA) inhibits human cytomegalovirus (HCMV) maturation by blocking Golgi-dependent envelopment and glycoprotein processing. Early BFA treatment also halts viral DNA synthesis, preventing progeny production.
Area of Science:
- Virology
- Cell Biology
Background:
- Human cytomegalovirus (HCMV) is a significant pathogen requiring effective antiviral strategies.
- Understanding HCMV replication and maturation is crucial for developing new treatments.
Purpose of the Study:
- To investigate the effects of Brefeldin A (BFA) on HCMV maturation in human fibroblasts.
- To elucidate the specific stages of HCMV morphogenesis affected by BFA.
Main Methods:
- Ultrastructural analysis of infected cells.
- Biochemical assays to assess viral protein processing and DNA synthesis.
- Treatment of infected cells with BFA at different stages of the viral cycle.
Main Results:
- Short-term BFA exposure during late HCMV infection inhibited Golgi-dependent envelopment of nucleocapsids in the trans-Golgi network (TGN).
- BFA impaired normal processing of glycoprotein B but did not affect nuclear viral morphogenesis.
- Early BFA treatment inhibited HCMV DNA synthesis and viral progeny production.
- Cytotoxicity of BFA was ruled out as a confounding factor.
Conclusions:
- HCMV morphogenesis involves sequential budding at the nuclear envelope and the TGN.
- BFA disrupts critical late-stage HCMV maturation processes, particularly those dependent on the Golgi apparatus.
- BFA is a potent inhibitor of HCMV replication, affecting both maturation and early DNA synthesis.