Cellular immunity to herpesviruses and immunodeficiency virus. Research Summary Dr. Rappocciolo is interested in the area of human herpesvirus research, in particular in the immunopathology of human herpesvirus 8 (HHV8 or Kaposi's sarcoma associated herpesvirus, KSHV). Dr. Rappocciolo recent studies have identified DC-SIGN, a C-type lectin, as the main receptor used by HHV8 to infect dendritic cells,activated macrophages and B lymphocytes. Recently, she has shown that HHV-8 infects and replicates in two types of dermal resident dendritic cells,Langerhan's cells and dermal dendritic cells. She also described the use by HHV-8 of both langerin and Ephrin A2 receptor on Langerhans cells as entry receptors for the virus. These findings established the first in vitro model of HHV-8 infection of its natural target cells. Another area of research led by Dr. Rappocciolo is the study of the role of antigen presenting cells such as activated B cells and dendritic cells in the transmission of HIV to bystander T cells. Dr. Rappocciolo has shown that activated B cells express DC-SIGN and this molecule is used to bind and internalized HIV, and although B cells do not become productively infected with HIV, they are able to deliver it to bystander T lymphocytes. So far, B cells are not considered to be a reservoir for HIV-1, but these data demonstrate that they could play an important role in HIV-1 transmission and pathogenesis. Recently, Dr. Rappocciolo has studied the relationship between trans infection and HIV-1 disease progression. Strikingly, DC and B cells from patients able to naturally control HIV-1 disease progression, called controllers, do not transfer HIV-1 to bystander T cells and this defect seems to be related to lower contents of cellular cholesterol. These data have been recently confirmed and expanded in human macrophages from HIV non progressors. Currently, Dr. Rappocciolo's lab is working on the identification of soluble biomarkers of HIV disease progression as related to the modulation of cell cholesterol content. More recently, the work on the role of trans infeciton in the regulation of HIV disease has been expanded to define the importance of B cell mediated trans infection in the establishment of the HIV latent reservoir in a subsets of CD4T cells, the naive CD4 T cells. Her lab is now expanding on this seminal study to understand the interactions between B cells and CD4T cells subsets that lead to HIV transfer and the establishment of the latent reservoir.
1983 | University of Milan, Milan, Italy | PhD, Biological Sciences
Director IDM 3440 Vaccines and Immunity
CoDirector IDM 2525 Microbiology Seminar
Gerberick A, DeLucia DC, Piazza P, Alaoui-El-Azher M, Rinaldo CR, Sluis-Cremer N, Rappocciolo G.B Lymphocytes, but Not Dendritic Cells, Efficiently HIV-1 Trans Infect Naive CD4 + T Cells: Implications for the Viral Reservoir mBio mBio2021 Mar 9;12(2):e02998-20.Rappocciolo G, Sluis-Cremer N, Rinaldo CR. Efficient HIV-1 Trans Infection of CD4 + T Cells Occurs in the Presence of Antiretroviral Therapy Open Forum Infect Dis. 2019 May 24;6(7 DeLucia DC, Rinaldo CR, Rappocciolo G. Inefficient HIV-1 trans Infection of CD4+ T Cells by Macrophages from HIV-1 Nonprogressors Is Associated with Altered Membrane Cholesterol and DC-SIGN. J Virol. 2018 Jun 13;92(13):e00092-18Rappocciolo G, Jais M, Piazza PA, DeLucia DC, Jenkins FJ, Rinaldo CR Human Herpesvirus 8 Infects and Replicates in Langerhans Cells and Interstitial Dermal Dendritic Cells and Impairs Their Function J Virol 2017 Sep 27;91(20):e00909-17Rappocciolo G, Jais M, Piazza P, Reinhart TA, Berendam SJ, Garcia-Exposito L, Gupta P, Rinaldo CR. Alterations in cholesterol metabolism restrict HIV-1 trans infection in nonprogressors. mBio 2014 Apr 29;5(3):e01031-13Rappocciolo G, Hensler HR, Jais M, Reinhart TA, Pegu A, Jenkins FJ, Rinaldo CR Human herpesvirus 8 infects and replicates in primary cultures of activated B lymphocytes through DC-SIGN. J Virol. 2008 May;82(10):4793-806Rappocciolo G, Piazza P, Fuller CL, Reinhart TA, Watkins SC, Rowe DT, Jais M, Gupta P, Rinaldo CR. DC-SIGN on B lymphocytes is required for transmission of HIV-1 to T lymphocytes. PLoS Pathog. 2006 Jul;2(7):e70. doi: 10.1371Rappocciolo G, Jenkins FJ, Hensler HR, Piazza P, Jais M, Borowski L, Watkins SC, Rinaldo CR Jr DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages. J Immunol. 2006 Feb 1;176(3):1741-9.Complete citations: https://scholar.google.com/citations?hl=en&user=MIZKlPgAAAAJ