Elisa Vicenzi
e-mail: vicenzi.elisa AT hsr.it
affiliation: San Raffaele Scientific Institute
research area(s): Immunity And Infection, Molecular Biology
Course:
Basic and Applied Immunology
University/Istitution: Università Vita-Salute San Raffaele
University/Istitution: Università Vita-Salute San Raffaele
EDUCATION
1985: Specialist in Pharmacology Research, Department of Education of the Regional Government of Lombardia, "Mario Negri" Institute for Pharmacological Research, Milan, Italy.
1980: Doctor in Pharmaceutical Sciences, University of Ferrara, Italy.
POSTDOCTORAL TRAINING
2009-present: Head of Unit, San Raffaele Scientific Institute, Milan, Italy.
1993-2006: Senior Investigator, AIDS Immunopathogenesis Unit, , San Raffaele Scientific Institute, Milan, Italy.
1987-1993: Research associate, Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, USA.
1986-1987: Guest researcher in the Laboratory of Chemo-Prevention, NCI, NIH, Bethesda, USA.
1985-1986: Research fellow, Healthy University, Linkoping, Sweden.
GRANTS
2010-2014: European Community Collaborative Research Project FP-7: "Combined Highly Active Anti-retroviral Microbicides (CHAARM)".
2010-2012: Ministry of Health, Rome: "Jab1 and HIV: a potentially dangerous liaison"
2010-2013: Fondazione Cariplo, Milan: "Novel strategies of vaccine design to prevent emerging and pandemic influenza virus infections (NoFlu)".
2011-2012: Istituto Superiore di Sanità, Rome: "Influenza Universal Vaccine".
ACADEMIC APPOINTMENTS
2004-present: Professor, Basic Experimental Research Techniques Course, Degree Course in Biotechnology"; Università Vita-Salute San Raffaele Milan.
1985: Specialist in Pharmacology Research, Department of Education of the Regional Government of Lombardia, "Mario Negri" Institute for Pharmacological Research, Milan, Italy.
1980: Doctor in Pharmaceutical Sciences, University of Ferrara, Italy.
POSTDOCTORAL TRAINING
2009-present: Head of Unit, San Raffaele Scientific Institute, Milan, Italy.
1993-2006: Senior Investigator, AIDS Immunopathogenesis Unit, , San Raffaele Scientific Institute, Milan, Italy.
1987-1993: Research associate, Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, USA.
1986-1987: Guest researcher in the Laboratory of Chemo-Prevention, NCI, NIH, Bethesda, USA.
1985-1986: Research fellow, Healthy University, Linkoping, Sweden.
GRANTS
2010-2014: European Community Collaborative Research Project FP-7: "Combined Highly Active Anti-retroviral Microbicides (CHAARM)".
2010-2012: Ministry of Health, Rome: "Jab1 and HIV: a potentially dangerous liaison"
2010-2013: Fondazione Cariplo, Milan: "Novel strategies of vaccine design to prevent emerging and pandemic influenza virus infections (NoFlu)".
2011-2012: Istituto Superiore di Sanità, Rome: "Influenza Universal Vaccine".
ACADEMIC APPOINTMENTS
2004-present: Professor, Basic Experimental Research Techniques Course, Degree Course in Biotechnology"; Università Vita-Salute San Raffaele Milan.
Our research interest is focused primarily on HIV/AIDS and, in particular, on host restriction factors of HIV infection and replication. In this regard, HIV-1 infection and replication in target cells is dependent on multiple interactions between virus and host. Recent findings have highlighted the role of Interferon (IFN)-induced intracellular antiviral proteins referred to as restriction factors capable of interfering with retroviral replication at various steps of the viral life cycle. In a setting where ongoing attempts to develop an HIV-1 vaccine faces significant challenges, investigation of innate restriction factors to infection remains crucial for the development of novel therapeutic strategies against HIV-1/AIDS. In this context, we have discovered that IFN-inducible TRIM22, a protein belonging to the family of the Tripartite Motif proteins suppresses HIV-1 LTR-mediated transcription in both myeloid and lymphoid targets of HIV-1 infection through a Tat-independent mechanism, most likely affecting the NF-κB-independent axis of early transcriptional activation of HIV-1.
These are the key questions that we are addressing:
1. Does TRIM22 play a role in the maintenance of chronic/latent HIV-infection in a panel of chronically HIV infected cell lines?
2. Which is the mechanism of TRIM22 restriction on HIV transcription?
3. What are the cellular partners of TRIM22 potentially involved in this restriction?
4. Is there any accessory HIV gene that potentially counteracts TRIM22 restriction?
5. What is the role of TRIM22 in HIV infected individuals?
6. Could TRIM22 SNPs play a role in HIV disease progression?
The ultimate goal of this project is the discovery of novel cellular mechanism(s) that oppose HIV infection with the potential of being exploited in anti-HIV strategies.
The second area of our research is Influenza A viruses. Influenza A viruses infect a variety of hosts including humans in which they mainly cause pandemic or seasonal influenza. An influenza pandemic may occur when a new influenza virus appears against which the human population has no immunity. To date, only viruses of the haemagglutinin (HA) H1, H2, H3 subtypes have caused pandemics in humans, and all pandemic viruses emerging in the 20th century had an avian progenitor virus donating at least the HA gene. Currently, other zoonotic subtypes of HA, such as H5, H7 and H9, are also considered potentially pandemic strains. There is significant antigenic difference both among and within subtypes that requires an annual update of the antigenic properties of the seed virus to be included in seasonal vaccines and generates concerns on the emergence of a pandemic strain with an antigenically different HA of an unpredictable subtype. The development of vaccines for influenza pandemic preparedness is focussed on either subtype-specific vaccines (for current seasonal influenza vaccines) or on panreactive vaccines based on cross-protective epitopes of HA or other highly conserved influenza proteins such as NP, M1, M2, among others.
To achieve the goal of constructing panreactive influenza vaccines, a multi-step research plan based on the following points:
It is crucial to evaluate the cross-protection between antibodies (Abs) against both human HA H1, H2 and H3 viruses and contemporary homo-subtypic avian viruses as well as to identify the prototype seed strains for vaccine production. To this end, pandemic and seasonal vaccine cohorts will be established and the Ab responses will be used as benchmark to assess cross-reactivity to selected animal viruses of the H1, H2, H3 subtype belonging to different lineages.
High throughput interrogation of human memory B cells and plasma cells will be performed to isolate rare Abs with broad neutralizing capacity. Sequencing and cross-reactivity information generated by the analysis of selected animal viruses will be integrated with the data generated by the epitope mapping of the clonal B cell memory repertoire. The analysis described above will lead to the design of modified HA proteins enriched in broadly neutralizing epitopes.
These are the key questions that we are addressing:
1. Does TRIM22 play a role in the maintenance of chronic/latent HIV-infection in a panel of chronically HIV infected cell lines?
2. Which is the mechanism of TRIM22 restriction on HIV transcription?
3. What are the cellular partners of TRIM22 potentially involved in this restriction?
4. Is there any accessory HIV gene that potentially counteracts TRIM22 restriction?
5. What is the role of TRIM22 in HIV infected individuals?
6. Could TRIM22 SNPs play a role in HIV disease progression?
The ultimate goal of this project is the discovery of novel cellular mechanism(s) that oppose HIV infection with the potential of being exploited in anti-HIV strategies.
The second area of our research is Influenza A viruses. Influenza A viruses infect a variety of hosts including humans in which they mainly cause pandemic or seasonal influenza. An influenza pandemic may occur when a new influenza virus appears against which the human population has no immunity. To date, only viruses of the haemagglutinin (HA) H1, H2, H3 subtypes have caused pandemics in humans, and all pandemic viruses emerging in the 20th century had an avian progenitor virus donating at least the HA gene. Currently, other zoonotic subtypes of HA, such as H5, H7 and H9, are also considered potentially pandemic strains. There is significant antigenic difference both among and within subtypes that requires an annual update of the antigenic properties of the seed virus to be included in seasonal vaccines and generates concerns on the emergence of a pandemic strain with an antigenically different HA of an unpredictable subtype. The development of vaccines for influenza pandemic preparedness is focussed on either subtype-specific vaccines (for current seasonal influenza vaccines) or on panreactive vaccines based on cross-protective epitopes of HA or other highly conserved influenza proteins such as NP, M1, M2, among others.
To achieve the goal of constructing panreactive influenza vaccines, a multi-step research plan based on the following points:
It is crucial to evaluate the cross-protection between antibodies (Abs) against both human HA H1, H2 and H3 viruses and contemporary homo-subtypic avian viruses as well as to identify the prototype seed strains for vaccine production. To this end, pandemic and seasonal vaccine cohorts will be established and the Ab responses will be used as benchmark to assess cross-reactivity to selected animal viruses of the H1, H2, H3 subtype belonging to different lineages.
High throughput interrogation of human memory B cells and plasma cells will be performed to isolate rare Abs with broad neutralizing capacity. Sequencing and cross-reactivity information generated by the analysis of selected animal viruses will be integrated with the data generated by the epitope mapping of the clonal B cell memory repertoire. The analysis described above will lead to the design of modified HA proteins enriched in broadly neutralizing epitopes.
Kajaste-Rudnitski, A., Marelli, S., Pultrone, C., Pertel, T., Uchil, P.D., Mechti, N., Mothes, W., Poli, G., Luban, J. & Vicenzi, E. (2011) TRIM22 Inhibits HIV-1 Transcription Independently of Its E3-Ubiquitin Ligase Activity, Tat and NF-{kappa}B Responsive LTR Elements. J Virol, 85:5183-5196.
Kajaste-Rudnitski, A., Galli, L., Nozza, S., Tambussi, G., Di Pietro, A., Pellicciotta, G., Monti, A., Mascagni, P., Moro, M. & Vicenzi, E. (2011) Induction of protective antibody response by MF59-adjuvanted 2009 pandemic A/ H1N1v Influenza Vaccine in HIV-1 Infected Individuals. AIDS, 25:177-183.
Kajaste-Rudnitski, A., Pultrone, C., Marzetta, F., Ghezzi, S., Coradin, T., Vicenzi, E .(2010) Restriction factors of retroviral replication: the example of Tripartite Motif (TRIM) protein 5 alpha and 22. Amino Acids. 39:1-9.
Capua, I., Kajaste-Rudnitski, A., Bertoli, E. & Vicenzi, E. (2009) Pandemic vaccine preparedness-have we left sominthing behind? Plos Pathogens, Jun;5(6):e1000482.
Rusnati, M., Vicenzi, E., Donalisio, M., Oreste, P. & Lembo, D. (2009) Sulfated K5 Escherichia coli polysaccharide derivatives: a novel class of candidate antiviral microbicides. Pharmacology & Therapeutics, 123:310-322.
Pinna, D., Oreste, P., Coradin, T., Kajaste-Rudnitski, A., Ghezzi, S., Zoppetti, G., Rotola, A., Argnani, R., Poli, G., Manservigi, R. & Vicenzi, E. Inhibition of Herpes Simplex Virus Type 1 and 2 In Vitro Infection by Sulfated Derivatives of K5 Escherichia coli Polysaccharide. (2008) Antimicrob Agents Chemother, 5:3078-3084.
Pacciarini, F., Ghezzi, S., Canducci, F., Sims, A., Sampaolo, M., Ferioli, E., Clementi, M., Poli, G., Conaldi, P.G., Baric, R. & Vicenzi, E. (2008) Persistent replication of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in human tubular kidney cells selects for adaptive mutations in the membrane protein. J Virol, 82:5137-5144.
Kajaste-Rudnitski, A., Galli, L., Nozza, S., Tambussi, G., Di Pietro, A., Pellicciotta, G., Monti, A., Mascagni, P., Moro, M. & Vicenzi, E. (2011) Induction of protective antibody response by MF59-adjuvanted 2009 pandemic A/ H1N1v Influenza Vaccine in HIV-1 Infected Individuals. AIDS, 25:177-183.
Kajaste-Rudnitski, A., Pultrone, C., Marzetta, F., Ghezzi, S., Coradin, T., Vicenzi, E .(2010) Restriction factors of retroviral replication: the example of Tripartite Motif (TRIM) protein 5 alpha and 22. Amino Acids. 39:1-9.
Capua, I., Kajaste-Rudnitski, A., Bertoli, E. & Vicenzi, E. (2009) Pandemic vaccine preparedness-have we left sominthing behind? Plos Pathogens, Jun;5(6):e1000482.
Rusnati, M., Vicenzi, E., Donalisio, M., Oreste, P. & Lembo, D. (2009) Sulfated K5 Escherichia coli polysaccharide derivatives: a novel class of candidate antiviral microbicides. Pharmacology & Therapeutics, 123:310-322.
Pinna, D., Oreste, P., Coradin, T., Kajaste-Rudnitski, A., Ghezzi, S., Zoppetti, G., Rotola, A., Argnani, R., Poli, G., Manservigi, R. & Vicenzi, E. Inhibition of Herpes Simplex Virus Type 1 and 2 In Vitro Infection by Sulfated Derivatives of K5 Escherichia coli Polysaccharide. (2008) Antimicrob Agents Chemother, 5:3078-3084.
Pacciarini, F., Ghezzi, S., Canducci, F., Sims, A., Sampaolo, M., Ferioli, E., Clementi, M., Poli, G., Conaldi, P.G., Baric, R. & Vicenzi, E. (2008) Persistent replication of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in human tubular kidney cells selects for adaptive mutations in the membrane protein. J Virol, 82:5137-5144.
Project Title:
TRIM22. A novel controller of HIV expression
TRIM (tripartite motif)-containing super family proteins are emerging as key components of a broad innate immune response against pathogens (Ozato et al. 2008). Among the 72 family members, we are interested in TRIM22 as an interferon-induced anti-HIV effector molecule. Overexpression of TRIM22 has been found to inhibit HIV-1 transcription in COS cells (Tissot and Mechti 1995) and infection in CD4/CCR5 expressing-293T cells and macrophages (Bouazzaoui et al. 2006). More recently, TRIM22 has been shown to be a key mediator of the interferon (IFN) response by inhibiting late steps in the HIV life cycle (Barr et al. 2008). However, we have demonstrated that TRIM22 inhibits basal as well as cytokine induced-HIV transcription consistently with TRIM22 nuclear localization (Kajaste-Rudnitski et al. 2011). In addition, we have identified two naturally occurring allelic variants that harbor distinct HIV-1 restriction capacities in vitro. These single nucleotide polymorphisms (SNPs) are located in the coding sequence of TRIM22 and result in non-synonymous amino acid substitutions.
The objectives of this project are focused to:
1. Evaluate whether TRIM22 plays a role in the maintenance of chronic/latent HIV-infection in a panel of chronically HIV infected cell lines;
2. Discover the mechanism of TRIM22 restriction on HIV transcription;
3. Identify cellular partner potentially involved in the HIV restriction;
4. Identify accessory HIV genes that potentially counteract TRIM22 restriction
5. Association study of TRIM22 SNPs with HIV disease progression.
The ultimate goal of this project is the discovery of novel cellular mechanism(s) that oppose HIV infection with the potential of being exploited in anti-HIV strategies.
The objectives of this project are focused to:
1. Evaluate whether TRIM22 plays a role in the maintenance of chronic/latent HIV-infection in a panel of chronically HIV infected cell lines;
2. Discover the mechanism of TRIM22 restriction on HIV transcription;
3. Identify cellular partner potentially involved in the HIV restriction;
4. Identify accessory HIV genes that potentially counteract TRIM22 restriction
5. Association study of TRIM22 SNPs with HIV disease progression.
The ultimate goal of this project is the discovery of novel cellular mechanism(s) that oppose HIV infection with the potential of being exploited in anti-HIV strategies.