Generation of a latency-deficient gammaherpesvirus that is protective against secondary infection.
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.
Rickabaugh
Tammy M
TM
Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA.
Brown
Helen J
HJ
Martinez-Guzman
DeeAnn
D
Wu
Ting-Ting
TT
Tong
Leming
L
Yu
Fuqu
F
Cole
Steven
S
Sun
Ren
R
D000818:Animals; D002460:Cell Line; D005260:Female; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000517:prevention & control / Q000821:virology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D018144:Rhadinovirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D015163:Superinfection / Q000517:prevention & control* / Q000821:virology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014611:Vaccination; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D017735:Virus Latency / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
D017874:Immediate-Early Proteins; D016328:NF-kappa B; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014764:Viral Proteins