title: Induction of protective immunity against murine gammaherpesvirus 68 infection in the absence of viral latency.
abstract: Human gammaherpesviruses, Epstein-Barr virus, and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus are important pathogens associated with diseases, including lymphomas and other malignancies. Murine gammaherpesvirus 68 (MHV-68) is used as an experimental model system to study the host immune control of infection and explore novel vaccine strategies based on latency-deficient live viruses. We studied the properties and the potential of a recombinant MHV-68 (AC-RTA) in which the genes required for persistent infection were replaced by a constitutively expressed viral transcription activator, RTA, which dictates the virus to lytic replication. After intranasal infection of mice, replication of AC-RTA in the lung was attenuated, and no AC-RTA virus or viral DNA was detected in the isolated splenocytes, indicating a lack of latency in the spleen. Infection of the AC-RTA virus elicited both cellular immune responses and virus-specific IgG at a level comparable to that elicited by infection of the wild-type virus. Importantly, vaccination of AC-RTA was able to protect mice against subsequent challenge by the wild-type MHV-68. AC-RTA provides a vaccine strategy for preventing infection of human gammaherpesviruses. Furthermore, our results suggest that immunity to the major latent antigens is not required for protection.
authors.affiliation: Department of Molecular and Medical Pharmacology, School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Qingmei
authors.initials: Q
authors.lastname: Jia
authors.forename: Michael L
authors.initials: ML
authors.lastname: Freeman
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Yager
authors.forename: Ian
authors.initials: I
authors.lastname: McHardy
authors.forename: Leming
authors.initials: L
authors.lastname: Tong
authors.forename: DeeAnn
authors.initials: D
authors.lastname: Martinez-Guzman
authors.forename: Tammy
authors.initials: T
authors.lastname: Rickabaugh
authors.forename: Seungmin
authors.initials: S
authors.lastname: Hwang
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Blackman
authors.forename: Ren
authors.initials: R
authors.lastname: Sun
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Wu
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000276:immunology / Q000502:physiology; D006801:Humans; D007109:Immunity / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018144:Rhadinovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D013154:Spleen / Q000821:virology; D014611:Vaccination; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D017735:Virus Latency / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D014764:Viral Proteins