Abstract

Herpesvirus saimiri is an oncogenic herpesvirus of New World primates. We will use h.
s aimi ri as a representative of the gamma herpesviruses to express SIV antigens for vaccine purposes. We have chosen h.
s aimi ri because it is distinct from herpes simplex virus, an alpha herpesvirus, because of its ability to infect rhesus monkeys and for the relative ease with which its genome can be manipulated. We will first identify an appropriate h.
s aimi ri gene that, when deleted, yields replication- competent, nonpathogenic virus that is able to persist in rhesus monkeys. Candidate genes based on previous studies include STP (saimiri transformation-associated protein), ORF-1, v-cyclin and superantigen homolog. We will then construct recombinant h.
s aimi ri strains expressing SIV antigens by replacing the selected target gene with an SIV gene or genes. Recombinant strains expressing SIV env, gag-pol, and env+gag-pol will be separately constructed and analyzed. H.
s aimi ri and SV40 promoters will be compared for their ability to direct SIV antigen expression from within the h.
s aimi ri genome. Well-characterized, recombinant h.
s aimi ri strains expressing SIV antigens derived from these studies will be used for vaccine testing in the project by Ronald C. Desrosiers.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI038131-04
Application #
6099939
Study Section
Project Start
1998-05-01
Project End
1999-06-30
Budget Start
Budget End
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Liang, Xiaozhen; Shin, Young C; Means, Robert E et al. (2004) Inhibition of interferon-mediated antiviral activity by murine gammaherpesvirus 68 latency-associated M2 protein. J Virol 78:12416-27
Feng, Pinghui; Scott, Christopher W; Cho, Nam-Hyuk et al. (2004) Kaposi's sarcoma-associated herpesvirus K7 protein targets a ubiquitin-like/ubiquitin-associated domain-containing protein to promote protein degradation. Mol Cell Biol 24:3938-48
Lee, Sun-Hwa; Chung, Young-Hwa; Cho, Nam-Hyuk et al. (2004) Modulation of T-cell receptor signal transduction by herpesvirus signaling adaptor protein. Mol Cell Biol 24:5369-82
Chung, Young-Hwa; Cho, Nam-hyuk; Garcia, Maria Ines et al. (2004) Activation of Stat3 transcription factor by Herpesvirus saimiri STP-A oncoprotein. J Virol 78:6489-97
Gwack, Yousang; Baek, Hwa Jin; Nakamura, Hiroyuki et al. (2003) Principal role of TRAP/mediator and SWI/SNF complexes in Kaposi's sarcoma-associated herpesvirus RTA-mediated lytic reactivation. Mol Cell Biol 23:2055-67
Nakamura, Hiroyuki; Lu, Michael; Gwack, Yousang et al. (2003) Global changes in Kaposi's sarcoma-associated virus gene expression patterns following expression of a tetracycline-inducible Rta transactivator. J Virol 77:4205-20
Gwack, Yousang; Nakamura, Hiroyuki; Lee, Sun Hwa et al. (2003) Poly(ADP-ribose) polymerase 1 and Ste20-like kinase hKFC act as transcriptional repressors for gamma-2 herpesvirus lytic replication. Mol Cell Biol 23:8282-94
Park, Junsoo; Cho, Nam-Hyuk; Choi, Joong-Kook et al. (2003) Distinct roles of cellular Lck and p80 proteins in herpesvirus saimiri Tip function on lipid rafts. J Virol 77:9041-51
Park, Junsoo; Lee, Bok-Soo; Choi, Joong-Kook et al. (2002) Herpesviral protein targets a cellular WD repeat endosomal protein to downregulate T lymphocyte receptor expression. Immunity 17:221-33
Means, R E; Choi, J K; Nakamura, H et al. (2002) Immune evasion strategies of Kaposi's sarcoma-associated herpesvirus. Curr Top Microbiol Immunol 269:187-201

Showing the most recent 10 out of 27 publications