Induction of protective immunity against murine gammaherpesvirus 68 infection in the absence of viral latency

Qingmei Jia, Michael L. Freeman, Eric J. Yager, Ian Howard Mchardy, Leming Tong, Dee Ann Martinez-Guzman, Tammy Rickabaugh, Seungmin Hwang, Marcia A. Blackman, Ren Sun, Ting Ting Wu

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2453-2465
Number of pages13
JournalJournal of Virology
Volume84
Issue number5
DOIs
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Immunology
  • Virology

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    Jia, Q., Freeman, M. L., Yager, E. J., Mchardy, I. H., Tong, L., Martinez-Guzman, D. A., Rickabaugh, T., Hwang, S., Blackman, M. A., Sun, R., & Wu, T. T. (2010). Induction of protective immunity against murine gammaherpesvirus 68 infection in the absence of viral latency. Journal of Virology, 84(5), 2453-2465. https://doi.org/10.1128/JVI.01543-09