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Member Information
Guido Silvestri, MD
Associate Professor of Pathology
Department of Pathology
Office Phone: 215-5735363
Office Fax: 215-5735369
Email: gsilvest@mail.med.upenn.edu
Website(s): http://www.med.upenn.edu/micro/faculty/silvestri.html
Education: M.D. 1987, University of Ancona
Keywords: HIV/AIDS, T cells, apoptosis, natural SIV hosts, cell cycle
Research and/or Clinical Interests:
Dr. Silvestri's research interest is on HIV/AIDS pathogenesis and vaccines. His clinical role is Director of the Clinical Virology at HUP.
Summary:
Our laboratory is interested in understanding the pathogenesis of the AIDS-associated depletion of CD4+ T lymphocytes. In particular, we are interested in the mechanisms by which SIV infection of natural hosts, such as the sooty mangabeys (an African monkey species) is not followed by CD4+ T cell depletion and AIDS despite chronic high levels of viral replication. This circumstance is strikingly different from the HIV infection of humans, or the SIV infection of non-natural hosts, i.e. rhesus macaques. Our studies focus on the host determinants that determine the rate of T cell depletion and progression to AIDS, and on the role that the host cellular immune responses play in suppressing virus replication, or alternatively, in inducing pathogenic consequences. We plan to apply these concepts to (i) the development of new, immune-based therapies for HIV infection (i.e., IL-2, IL-7) to be used in addition to standard antiretroviral therapy, and (ii) the design of T-cell-based AIDS vaccines that will generate memory T cell responses against HIV/SIV that may confer significant protection while not inducing any relevant immunopathology.
Representative Publications (2002-current):
Schindler M, Münch J, Kutsch O, Li H, Santiago M, Bibollet-Ruche F, Müller-Trutwin MC, Novembre FJ, Peeters M, Courgnaud V, Bailes E, Roques P, Sodora DL, Silvestri G, Sharp PM, Hahn BH, Kirchhoff F. Nef-mediated suppression of T cell activation is a fundamental property of primate lentiviruses that was lost in the lineage that gave rise to HIV-1 Cell, (in press)
Dunham R, Pagliardini P, Gordon S. Sumpter B, Engram J, Moanna A, McClure H, Ibegbu C, Katz N, Pandrea I, Apetrei C, Sodora D, Feinberg M, Staprans SI, Silvestri G. The AIDS-resistance of naturally SIV-infected sooty mangabeys is independent of cellular immunity to the virus. Blood, (in press)
Paiardini M, Cervasi B, Sumpter B, McClure H, Magnani M, Staprans SI, Piedimonte G, Silvestri G. Perturbations of cell cycle control in T cells are involved in determining the different outcomes of SIV-infection in rhesus macaques and sooty mangabeys. J Virol, 2006, 80:634-42.
Derdeyn C, Silvestri G. Viral and host factors in the pathogenesis of HIV infection. Curr Opin Immunol, 2005, 17:366-73.
Silvestri G, Fedanov A, Germon S, Kozyr W, Kaiser WJ, McClure HM, Feinberg MF, Staprans S. Divergent host response during primary SIVsmm infection of natural and non-natural hosts. J Virol, 2005, 79:4043-4054.
Paiardini M, Cervasi B, Albrecht H, Muthukumar A, Dunham R, Gordon S, Piedimonte G, Magnani M, Radziewicz H, Weintrob A, Montroni M, Kaech SM, Altman JD, Sodora DL, Feinberg MB, Silvestri G. Loss of CD127 (interleukin-7 receptor) defines an expansion of CD8+ effector T cells in HIV-infected patients. J Immunol, 2005, 174:2900-9.
Garber DA, Silvestri G, Barry A, Fedanov A, Kozyr N, McClure H, Montefiori D, Larsen CP, Altman JD, Staprans S, Feinberg MB. Blockade of T-cell costimulation reveals interrelated actions of CD4+ and CD8+ T-cells in control of SIV replication. J Clin Invest, 2004, 113:836-845.
Galati D, Paiardini M, Cervasi B, Albrecht H, Bocchino ML, Costantini A, Montroni M, Piedimonte G, Magnani M, Silvestri G. Post-translational regulation of nucleolin in the cell cycle disease of HIV-infected patients. J Infect Dis, 2003, 188:1483-1491
Silvestri G, Sodora DL, Koup RA, O'Neil SP, Paiardini M, McClure HM, Staprans S,
Feinberg MB . Non-pathogenic simian immunodeficiency virus infection of sooty mangabeys is characterized by limited bystander immunopathology despite high levels viral replication. Immunity, 2003, 18: 341-352
Liu L, Charoudi A, Silvestri G, Wernett M, Kaiser WJ, Safrit JT, Komoriya A, Altman JD, Packard BZ, Feinberg MB. Visualization and quantitation of T-cell mediated cytotoxicity using cell-permeable fluorogenic caspase substrates. Nature Medicine, 2002 8:185-189
