Mosier Laboratory Homepage

Viral Immunity and Pathogenesis

Don Mosier Ph.D., M.D., Member/Professor Our laboratory focuses on animal models for important viral diseases of humans. We study immunity to and the pathogenesis of diseases caused by the human immunodeficiency virus (HIV-1), Epstein-Barr virus (EBV), and human herpesvirus 8/Kaposi's Sarcoma-associated herpesvirus (HHV8/KSHV). We use mice with severe combined immune deficiency (SCID) as recipients of human cells or tissues. The most common source of cells is human peripheral blood leukocytes, and mice grafted with these cells are called hu-PBL-SCID mice. These mice are susceptible to infection with HIV-1 and suffer the same loss of human CD4 T cells seen in infected individuals. Antibody and cytotoxic T lymphocytes (CTL) can each provide some protection against HIV-1 infection. EBV can also infect hu-PBL-SCID mice, and it leads to transformation of B cells and a disease similar to post-tranplant or AIDS-associated lymphoma. Recent efforts focus on the development of antiviral compounds targetting the CCR5 coreceptor for HIV-1 entry and preclinical vaccine studies to define the basis of protective immunity to HIV-1. The recapitulation of human diseases in a mouse model system provides many opportunities for examining effector mechanisms in immunity and the viral determinants of disease progression.

Personnel:

Donald E. Mosier, Ph.D., M.D., Member/Professor  dmosier@scripps.edu
Christina Pastore, Ph.D., Senior Research Associate  cpastore@scripps.edu
Manisha Yadav, Ph.D., Research Associate cmanisha@scripps.edu
Alejandra Ramos, Research Assistant  alejandr@scripps.edu
Gregory Franklin, Research Assistant gfrankli@scripps.edu

Recent Publications

Pastore, C, G.R. Picchio, F. Galimi, R. Fish, O. Hartley, R.E. Offord and D.E. Mosier. 2003. Two mechanisms for human immunodeficiency virus type I inhibition by N-terminal modifications of RANTES. Antimicrob. Agents Chemother. 47:509-517.

Sabbe, R., G.R. Picchio, C. Pastore, O. Chaloin, O. Hartley, R.E. Offord and D.E. Mosier. 2001. Donor- and ligand-dependent differences in C-C chemokine receptor 5 reexpression. J. Virol. 75:661-671.

Mosier, D.E., G.R. Picchio, R.J. Gulizia, R. Sabbe, P. Poignard, L. Picard, R.E. Offord, D.A. Thompson and J. Wilken. 1999. Highly potent RANTES analogues either prevent CCR5-using human immunodeficiency virus type I infection in vivo or rapidly select for CXCR4-using variants. J. Virol. 73:3544-3550.

Poignard, P., R. Sabbe, G.R. Picchio, M. Wang, R.J. Gulizia, H. Katinger, P. Parren, D.E. Mosier and D. R. Burton. 1999. Neutralizing antibodies have limited effects of the control of established HIV-1 infection in vivo. Immunity. 10:1-20.

Picchio, G.R., R.J. Gulizia, and D.E. Mosier. 1997. Chemokine receptor CCR5 genotype influences the kinetics of human immunodeficiency virus type 1 infection in human PBL-SCID mice. J Virol 71:7124-7127.

Gulizia, R.J., R.G. Collman, J.A. Levy, D. Trono, and D.E. Mosier. 1997. Deletion of nef slows but does not prevent CD4-positive T-cell depletion in human immunodeficiency virus type 1-infected human-PBL-SCID mice. J Virol 71:4161-4164.

Mosier, D. 1996. Viral pathogenesis in hu-PBL-SCID mice. Seminars Immunol 8:255-262.