Induction of protective immunity against murine gammaherpesvirus 68 infection in the absence of viral latency.
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.
Jia
Qingmei
Q
Department of Molecular and Medical Pharmacology, School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
Freeman
Michael L
ML
Yager
Eric J
EJ
McHardy
Ian
I
Tong
Leming
L
Martinez-Guzman
DeeAnn
D
Rickabaugh
Tammy
T
Hwang
Seungmin
S
Blackman
Marcia A
MA
Sun
Ren
R
Wu
Ting-Ting
TT
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
D000956:Antigens, Viral; D014764:Viral Proteins