Generation of a latency-deficient gammaherpesvirus that is protective against secondary infection.
Title | Generation of a latency-deficient gammaherpesvirus that is protective against secondary infection. |
Publication Type | Journal Article |
Year of Publication | 2004 |
Authors | Rickabaugh TM, Brown HJ, Martinez-Guzman DA, Wu T-T, Tong L, Yu F, Cole S, Sun R |
Journal | J Virol |
Volume | 78 |
Issue | 17 |
Pagination | 9215-23 |
Date Published | 2004 Sep |
ISSN | 0022-538X |
Keywords | Animals, Cell Line, Female, Gene Expression Regulation, Viral, Herpesviridae Infections, Humans, Immediate-Early Proteins, Kinetics, Lung, Mice, Mice, Inbred BALB C, NF-kappa B, Promoter Regions, Genetic, Rhadinovirus, Superinfection, Trans-Activators, Vaccination, Viral Proteins, Virus Latency, Virus Replication |
Abstract | Kaposi's sarcoma-associated herpesvirus and murine gammaherpesvirus-68 (MHV-68) establish latent infections and are associated with various types of malignancies. They are members of the gamma-2 herpesvirus subfamily and encode a replication and transcriptional activator, RTA, which is necessary and sufficient to disrupt latency and initiate the viral lytic cycle in vitro. We have constructed a recombinant MHV-68 virus that overexpresses RTA. This virus has faster replication kinetics in vitro and in vivo, is deficient in establishing latency, exhibits a reduction in the development of a mononucleosis-like disease in mice, and can protect mice against challenge by wild-type MHV-68. The present study, by using MHV-68 as an in vivo model system, demonstrated that RTA plays a critical role in the control of viral latency and suggests that latency is a determinant of viral pathogenesis in vivo. |
DOI | 10.1128/JVI.78.17.9215-9223.2004 |
Alternate Journal | J. Virol. |
PubMed ID | 15308716 |
PubMed Central ID | PMC506911 |
Grant List | CA83525 / CA / NCI NIH HHS / United States CA91791 / CA / NCI NIH HHS / United States DE14153 / DE / NIDCR NIH HHS / United States GM07185 / GM / NIGMS NIH HHS / United States |