Ivona Pandrea, MD, PhD Dr. Pandrea is an associate professor of Pathology and member of Division of Experimental Pathology. Office Location: Department of Pathology Center for Vaccine Research 9017 Biomedical Science Tower 3 3501 Fifth Avenue Pittsburgh, PA 15261 Contact Information: Office Phone: (412) 624 3242 Fax: 412 624 4440 Email Address: pandrea@pitt.edu Research Interests: Research in Pandrea's lab is aimed to understand why, despite their high prevalence of SIV infection, the African nonhuman primates generally do not progress to AIDS. We are particularly interested to understand how these nonhuman primate species are able to maintain normal levels of immune activation during SIV infection. We believe that, despite high viral replication, the low levels of immune activation and apoptosis allow mucosal CD4 T cell recovery and therefore nonprogression to AIDS in the natural hosts. Our major research directions are therefore aimed to: (i) study of the correlations between the low levels of CCR5 expression on the mucosal CD4+ T cells and the low levels of immune activation and mucosal SIV transmission (particularly through breast-feeding) in the natural hosts; (ii) understanding the role of the interaction between dendritic cells and T regulatory cells in maintaining low levels of immune activation in the nonprogressive hosts; (iii) investigating how microbial translocation impact immune activation and other systemic lesions in progressive and nonprogressive hosts; and (iv) testing new avenues to prevent the intestinal barrier damage or the damage induced by the proinflammatory cytokines released during the HIV infection. Our final goal is to identify new immunotherapeutic strategies that, in association to antiretroviral drugs, may ultimately transform HIV-1 infection into a nonprogressive infection with an incubation period that exceeds the human lifespan, similar to SIV infection in natural hosts. Selected Publications: Klatt NR, Shudo E, Ortiz AM, Engram JC, Paiardini M, Lawson B, Miller MD, Else J, Pandrea I, Estes JD, Apetrei C, Schmitz JE, Ribeiro RM, Perelson AS, Silvestri G: CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan ofproductively infected cells. Plos Pathogens, 2009: in press. Beaumier CM, Harris LD, Goldstein S, Klatt NR, Whitted S, McGinty J, Apetrei C, Pandrea I, Hirsch VM, Benchley JM: Down regulation of CD4 by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection. Nat Med 2009, 15; 879-885. Sodora DL, Allan JS, Apetrei C, Brenchley JM, Douek DC, Else JG, Estes JD, Hahn BH, Hirsch VM, Kaur A, Kirchhoff F, Muller-Trutwin M, Pandrea I, Schmitz JE, Silvestri G: Towards an AIDS vaccine: lessons from natural SIV infections of African nonhuman primate hosts. Nat Med 2009; 15: 861-865. Gautam R, Gaufin T, Gautam A, Butler I, Barnes M, Mandell D, Pattison M, Macfarland J, Monjure C, Tatum C, Pandrea I, and Apetrei C: SIVrcm, a unique CCR2-tropic virus, selectively depletes effector memory CD4+ T-cells in pigtailed macaques through rapid co-receptor expansion in vivo. J Virol, 2009; 83: 7894-7908. Gaufin T, Gautam R, Kasheta M, Ribeiro R, Ribka E, Barnes M, Pattison M, Tatum C, Monjure C, Montefiori D, Kaur A, Pandrea I, & Apetrei C: Limited impact of humoral immune responses on controlling viremia during rhesus macaque infection with the neutralization-sensitive strain SIVsmmD215. Blood, 2009; 113: 4250-4261. Pandrea I, Silvestri G, and Apetrei C: AIDS in African nonhuman primate hosts of SIVs: A new paradigm of SIV infection. Curr HIV Res 2009, 6: 57-72. Souquière S, Onanga R, Makuwa M, Pandrea I, Ngari P, Rouquet P, Bourry O, Kazanji M, Apetrei C, Simon F, & Roques P: SIVmnd-1 and SIVmnd-2 have different pathogenic potentials in rhesus macaques upon experimental cross-species transmission. J Gen Virol, 2009; 90: 488-499. Paiardini M, Pandrea I, Apetrei C, and Silvestri G: Lessons learned from the natural hosts of HIV-related viruses. Annu Rev Med. 2009: 60: 485-495. Pandrea I, Gaufin T, Brenchley JM, Gautam R, Monjure C, Gautam A, Coleman C, Lackner AA, Ribeiro RM, Douek DC, &Apetrei C: Cutting edge: Experimentally induced immune activation in natural hosts of simian immunodeficiency virus induces significant increases in viral replication and CD4+ T cell depletion. J Immunol. 2008, 181: 6687-91. Pandrea I, Sodora DL, Silvestri G, & Apetrei C: Into the wild: Simian immunodeficiency virus (SIV) infection in natural hosts. Trends Immunol; 2008; 29: 419-28. Pandrea I, Onanga R, Souquiere S, Mouinga-Ondéme A, Bourry O, Makuwa M, Rouquet P, Silvestri G, Simon F, Roques P & Apetrei C: Paucity of CD4+ CCR5 T-cells may prevent breastfeeding transmission of SIV in natural non-human primate hosts. J. Virol 2008; 82: 5501-5509. Paiardini M, Frank I, Apetrei C, Pandrea I, & Silvestri G: Mucosal immune dysfunction in AIDS pathogenesis. AIDS Reviews 2008; 10: 36-46. Pandrea I, Ribeiro RM, Gautam R, Gaufin T, Pattison M, Barnes M, Monjure C, Stoulig C, Silvestri G, Miller M, Perelson AS, & Apetrei C: Simian Immunodeficiency Virus SIVagm Dynamics in African Green Monkeys. J Virol 2008: 82: 3713-3724. Gordon SN, Dunham RM, Engram JC, Estes J, Klatt N, Pandrea I, Apetrei C, Sodora DL, Lee HY, Haase AT, Miller M, Kaur A, Staprans SI, Perelson AS, Feinberg MB, & Silvestri G: Short-lived infected cells support the bulk of virus replication in naturally SIV-infected sooty mangabeys: implications for AIDS pathogenesis. J Virol 2008; 82: 3725-3735. Coleman C, Apetrei C, Muller-Trutwin MC & Pandrea I: Tregs: Aid or Hindrance in the Clearance of Disease? J Cell Mol Med, 2007, 11: 1291-1325. Silvestri G, Paiardini M, Pandrea I, Lederman MM, Sodora DL: Understanding the benign nature of SIV infection in natural hosts. J Clin Invest. 2007 117: 3148-3154. Pandrea I, Gautam R, Ribeiro R, Brenchley JM, Barbercheck J, Butler IF, Rasmussen T, Marx PA, Silvestri G, Lackner AA, Perelson A, Douek DC, Veazey RS & Apetrei C: Acute loss of intestinal CD4+ T cells is not predictive for SIV virulence. J Immunol. 2007: 79:3035-46. Gordon S, Klatt NR, Milush J, Engram JC, Dunham RM, Paiardini M, Strobert EA, Apetrei C, Pandrea I, Staprans SI, Sodora DL & Silvestri G: Severe depletion of mucosal CD4+ T cells in AIDS-free SIV-infected mangabeys. J Immunol. 2007: 79:3026-34. Milush JM, Stefano-Cole K, Schmidt K, Durudas A, Pandrea I, Sodora DL: Mucosal Innate Immune Response Associated With A Timely Humoral Immune Response And Slower Disease Progression Following Oral Transmission of SIV In Rhesus Macaques. J Virol. 2007: 81:6175-86. Apetrei C, Gautam R, Sumpter B, Carter AC, Gaufin T, Staprans S, Else J, Barnes M, Cao B, Garg S, Milush J, Sodora DL, Pandrea I & Silvestri G: Virus-subtype specific features of natural SIVsmm infection in sooty mangabeys. J. Virol 2007: 81:7913-23. Gautam R, Katz N, Butler IF, Barnes M, Hasegawa A, Ratterree M, Silvestri G, Marx PA, Hirsch VM, Pandrea I, & Apetrei C: In vitro Characterization of Primary SIVsmm Isolates Belonging to Different Lineages. In Vitro growth on on Rhesus Macaque Cells is Not Predictive for in Vivo Replication in Rhesus Macaques. Virology, 2007, 362: 257-270. Butler IF, Pandrea I, Marx PA, Apetrei C: HIV genetic diversity: Biological and public health consequences Current HIV Res 2007: 5: 25-47. Pandrea I, Apetrei C, Gordon S, Barbercheck, Dufour J, Bohm R, Sumpter B, Roques P, Marx PA, Hirsch V, Kaur A, Lackner AA, Veazey RS & Silvestri G: Paucity of CD4+CCR5+ T-cells is a typical feature of natural SIV hosts Blood, 2007: 35:1069-76 Comment in Blood: Roeder M and