Giovanna Rappocciolo, PhD

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, and the role of miRNAs in the modulationof cell cholesterol pathways. These data could provide a better insight of the pathogenesis of HIV-1 infection. 

1983 | University of Milan, Milan, Italy | PhD, Biological Sciences

2.Rappocciolo 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;5(3):e01031-13. PMID:24781743. PMCID:PMC4010827.

3. Rappocciolo 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 pathogens. 2006 Jul;2(7):e70.

4.Rappocciolo 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 T.
Rappocciolo G, Jais M, Piazza PA, DeLucia DC, Jenkins FJ, Rinaldo CR.

5. Rappocciolo 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. Journal of immunology (Baltimore, Md. : 1950). 2006 Feb 1;176(3):1741-9. PMID:16424204.

6.Campbell DM, Rappocciolo G, Jenkins FJ, Rinaldo CR. Dendritic cells: key players in human herpesvirus 8 infection and pathogenesis. Frontiers in Microbiology. 2014;5:452. 

7. Rappocciolo 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. Journal of virology. 2008 May;82(10)

8.Knowlton ER, Rappocciolo G, Piazza P, Lepone LM, Nadgir SV, Bullotta A, Berendam SJ, Li J, Reinhart TA, Jenkins FJ, Rinaldo CR. Human Herpesvirus 8 Induces Polyfunctional B Lymphocytes That Drive Kaposi's Sarcoma. MBio. 2014;5(5)PMID:25182322. doi:10.1128/mBio.01277-14

9.Lepone L, Rappocciolo G, Knowlton E, Jais M, Piazza P, Kenkins FJ, Rinaldo CR. Monofunctional and polyfunctional CD8+ T cell responses to human herpesvirus 8 lytic and latency proteins. Clin Vaccine Immunol. 2010;17(10):1507-16. PMID:20719985. PMCID:2952991.1

 

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