A Gammaherpesvirus 68 Gene 50 Null Mutant Establishes Long-term Latency in the Lung but Fails to Vaccinate Against a Wild-type Virus Challenge.
From: Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University School of Medicine, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
Journal of virology
- Publish Date: Feb 2006
- ISSN: 0022-538X
- Volume: 80
- Issue: 3
- Pages: 1592-8
- Medium: Print
- Language: English
- Citation (JAMA): Moser Janice M, Farrell Michael L, Krug Laurie T, et al. A Gammaherpesvirus 68 Gene 50 Null Mutant Establishes Long-term Latency in the Lung but Fails to Vaccinate Against a Wild-type Virus Challenge.. J. Virol. Feb 2006;80:1592-8
Abstract
The gammaherpesvirus immediate-early genes are critical regulators of virus replication and reactivation from latency. Rta, encoded by gene 50, serves as the major transactivator of the lytic program and is highly conserved among all the gammaherpesviruses, including Epstein-Barr virus, Kaposi’s sarcoma-associated herpesvirus, and murine gammaherpesvirus 68 (gammaHV68). Introduction of a translation stop codon in gammaHV68 gene 50 (gene 50.stop gammaHV68) demonstrated that Rta is essential for virus replication in vitro. To investigate the role that virus replication plays in the establishment and maintenance of latency, we infected mice with gene 50.stop gammaHV68. Notably, the gene 50.stop virus established a long-term infection in lung B cells following intranasal infection of mice but was unable to establish latency in the spleen. This complete block in the establishment of latency in the spleen was also seen when lytic virus production was inhibited by treating mice infected with wild-type virus with the antiviral drug cidofovir, implicating virus replication and not an independent function of Rta in the establishment of splenic latency. Furthermore, we showed that gene 50.stop gammaHV68 was unable to prime the immune system and was unable to protect against a challenge with wild-type gammaHV68, despite its ability to chronically infect lung B cells. These data indicate gammaherpesviruses that are unable to undergo lytic replication in vivo may not be viable vaccine candidates despite the detection of cells harboring viral genome at late times postinfection.
Mesh Headings (Keywords): Animals, Antiviral Agents, Codon, Terminator, Cytosine, Genes, Viral, Herpesvirus Vaccines, Humans, Lung, Mice, Mice, Inbred C57BL, Mutation, Phosphonic Acids, Rhadinovirus, Trans-Activators, Vaccination, Viral Proteins, Virus Latency
Check for Full Text / PubMed Unique Identifier (PMID): 16415035
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.