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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Integration of bovine herpesvirus 4 genome into cultured persistently infected host cell genome
Gaetano Donofrio1, Antonio Capocefalo, Valentina Franceschi
1Dipartimento di Salute Animale, Sezione di Malattie Infettive degli Animali, Università di Parma, Via del Taglio 10, 43100 Parma, Italy. gaetano.donofrio@unipr.it
Abstract:
Persistent infection of macrophages with bovine herpesvirus 4 (BoHV-4) has been proposed to play a secondary causal role, along with bacterial infection, in bovine post-partum metritis. Mechanisms of maintenance of BoHV-4 persistent infection are not understood. We previously generated in vitro models of BoHV-4 persistent infection in human rhadomyosarcoma and bovine macrophage cell lines by drug selection of cells infected with BoHV-4 carrying a drug-resistance marker, and demonstrated circular episomal BoHV-4 genomes. In the present study, we used fluorescent in situ hybridization (FISH) to demonstrate BoHV-4 genomes also integrated into the genomes of these persistently infected cells.
Insights
Persistent bovine herpesvirus 4 (BoHV-4) infection in macrophages, linked to bovine metritis, involves both circular episomal and integrated viral genomes. Understanding these mechanisms is crucial for controlling persistent infections.
Area of Science:
- Veterinary Virology
- Cellular Microbiology
- Infectious Diseases
Background:
- Bovine herpesvirus 4 (BoHV-4) persistent infection in macrophages is implicated in bovine post-partum metritis.
- The mechanisms maintaining BoHV-4 persistent infection remain unclear.
- Previous studies established in vitro models using drug-selected cells with circular episomal BoHV-4 genomes.
Purpose of the Study:
- To investigate the genomic state of BoHV-4 during persistent infection in macrophages.
- To elucidate mechanisms of BoHV-4 genome maintenance in host cells.
Main Methods:
- Generation of in vitro models of persistent BoHV-4 infection in human and bovine macrophage cell lines.
- Drug selection of infected cells carrying a BoHV-4 drug-resistance marker.
- Fluorescent in situ hybridization (FISH) to detect viral genomes within host cell nuclei.
Main Results:
- Demonstration of circular episomal BoHV-4 genomes in persistently infected cells.
- Confirmation of BoHV-4 genome integration into the host cell genome using FISH.
- Evidence for dual genomic states (episomal and integrated) of BoHV-4 during persistent infection.
Conclusions:
- BoHV-4 persistent infection in macrophages is characterized by the presence of both circular episomal and integrated viral genomes.
- Genome integration represents a potential mechanism for long-term persistence of BoHV-4.
- Further research is needed to fully understand the implications of these genomic states for disease pathogenesis.
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