Guido Poli
Guido Poli
affiliation: Università Vita-Salute San Raffaele
research area(s): Immunity And Infection, Experimental Medicine
Course: Basic and Applied Immunology
University/Istitution: Università Vita-Salute San Raffaele
1982: Medical Doctor, University of Ferrara, Italy (Summa cum laude)
1985: Specialist in Oncology, University of Ferrara, Italy (Summa Cum Laude)
1983-1986: Research fellow in the Laboratory of Human Immunology (Chief: Dr. Alberto Mantovani), "Mario Negri" Institute for Pharmacological Research, Milano, Italy
1987-1993: Laboratory of Immunoregulation (Chief: Dr. Anthony S. Fauci), National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA. Final position: Visiting Scientist.
From 1994: Head, AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, Milano, Italy.
From 2002: Associate Professor of Pathology and Immunology,
Vita-Salute San Raffaele University School of Medicine, Milano, Italy.

1992: NIH Award of Merit.
1999: European Society for Clinical Investigation (ESCI) Award

2001-2005: Associate Editor, The Journal of Immunology
Since 2004: Editorial Board, Medicinal Chemistry, Drug Design Reviews " Online
Since 2005: Associate Editor, AIDS
Since 2008: Editorial Board, The Open AIDS Journal, The Open Immunology Journal, The Open Virology Journal

From 2008: Coordinator, Basic and Applied Immunology Section, International Graduate School in Molecular Medicine, Vita-Salute San Raffaele University School of Medicine, Milano, Italy.
From 2011: Coordinator, "CellDiff", Centre of Excellence of the Vita-Salute San Raffaele University School of Medicine, Milano, Italy.

- Vice-Director for Italy of the Global Viral Network, chaired by Robert C. Gallo, Institute of Human Virology, Baltimore, MD, USA (

- Co-Chair, Subgroup "Immunological mechanisms and compartments involved", "TOWARDS AN HIV CURE": GLOBAL SCIENTIFIC STRATEGY International Working Group, Chaired by Francoise Barré-Sinoussi (Nobel Prize 2008 for the discovery of HIV) (

Bibliometry (JCR 2008)
ORIGINAL ARTICLES: 136 (IF: 834,709)
TOTAL: 216 (IF: 1.007,12)

h Index (from ISI WOS, since 1990): 39

I have been involved in AIDS research since 1984 working with Alberto Mantovani on the defects of natural immunity (i.e. macrophages and NK cells) in infected individuals. I then moved to the NIH where I have been working with Tony Fauci from 1986 to 1993 and where my interest and expertise has focused on the role of cytokines as regulators of HIV expression. In these years, my main interest has been cytokine-mediated control of HIV latency in chronically infected cell lines. Several articles in prestigious journals (Science, J. Exp. Med, J. Immunol, J. Virol and others) have lead to a model where virtually every step of the virus life cycle is regulated, either positively or negatively, by cytokines or cytokine-related pathways. Returned to Italy as Head of the AIDS Immunopathogenesis Unit at the end of 1993, my resesearch interest has evolved in different directions. I have strong interest in understanding the alterations induced by HIV infection in vitro and in vivo in terms of cytokine-related signaling, with particular regard to the JAK/STAT pathway. In a very recent paper, we have demonstrated that HIV infected individuals are characterized by a constitutive activation of STAT-1 and STAT-5 in their PBMC (Blood, 94:4202, 1999) and, further, that the activated STAT-5 is predominantly a C-terminus truncated form likely acting as a transdominant negative mutant.

A. Crotti, M. Lusic, R. Lupo, P.M.J. Lievens, E. Liboi, G. Della Chiara, M. Tinelli, A. Lazzarin, B.K. Patterson, M. Giacca, C. Bovolenta, & G. Poli. 2007. Naturally occurring C-terminally truncated STAT5 is a negative regulator of human immunodeficiency virus-type 1 expression. Blood, 109:5380-5389.

E. Pilotti, L. Eviri, E. Vicenzi, U. Bertazzoni, M.C. Re, S. Allibardi, G. Poli, & C. Casoli. 2007. Post-genomic upregulation of CCL3L1 expression in HTLV-2 infected individuals curtails HIV-1 replication. Blood 109:1850-6.

M. Alfano, S.A. Mariani, C. Elia, R. Pardi, F. Blasi, & G. Poli. 2009. Ligand-engaged urokinase-type plasminogen activator receptor (uPAR) and the CD11b/CD18 (Mac1) integrin inhibit late events of HIV expression in monocytic cells. Blood, 113:1699-1709.

L. Cassetta, O. Fortunato, L. Adduce, C. Rizzi, J. Hering, P. Rovere-Querini, M.E. Bianchi, M. Alfano, & G. Poli. 2009. Extracellular HMGB1 inhibits R5 and X4 HIV-1 strains replication in mononuclear phagocytes without induction of chemokines and cytokines. AIDS, 23:567-578.

E. Cassol, C. Rizzi, L. Cassetta, M. Alfano, & G. Poli. 2009. M1 and M2a polarization of human monocyte-derived macrophages inhibits HIV-1 replication by distinct mechanisms. J. Immunol. 182: 6237-6246.

E. Cassol, S. Malfeld, S. van der Merwe, P. Mahasha, S. Cassol, C. Seebregts,
M. Alfano, G. Poli, & S. T. Rossouw. 2010. Persistent microbial translocation and immune activation in HIV-1-infected South Africans receiving combination antiretroviral therapy. J. Inf. Dis. 202:723-33.

Kajaste-Rudnitski, S.S. Marelli, C. Pultrone, T. Pertel, P.D. Uchil, N. Mechti, W. Mothes, G. Poli, J. Luban, & E. Vicenzi. 2011. TRIM22 inhibits HIV-1 transcription independently of its E3-ubiquitin ligase activity, Tat and NF-kB Responsive LTR elements. J. Virology, 85:5183-96.

G. Della Chiara, A. Crotti, E. Liboi, M. Giacca, G. Poli, & M. Lusic. 2011. Negative regulation of HIV-1 transcription by a heterodimeric NF-KappaB1 p50 and C-terminally truncated STAT5 complex. J. Mol. Biol., in press.


M. Alfano, A. Crotti, E. Vicenzi, & G. Poli. 2008. New players in cytokine control of HIV infection. Current HIV/AIDS Report, 5:27-32.

E. Cassol, L. Cassetta, C. Rizzi, M. Alfano, & G. Poli. 2010. Macrophage polarization and HIV-1 infection. J. Leuk. Biol., 87:599-608.

G. Poli & V. Erfle. Pathogenesis of Immunodeficiency virus infections. In: "Retroviruses: Molecular Microbiology and Genomics" (Eds. Reinhard Kurth and Norbert Bannert), Caister Academic Press, Norfolk, U.K. pp.269-283, 2010.

S.A. Mariani, E. Vicenzi & G. Poli. 2011. Asymmetric HIV-1 co-receptor use and replication in CD4+ T lymphocytes. J. Transl. Med., Jan 27;9 Suppl 1:S8.

Riva, E. Vicenzi, M. Galli & G. Poli. 2011. Strenuous resistance to natural HIV-1
disease progression. Viral controllers and long term non-progressors. Future Virology, 6(4): 521-533.

G. Poli. 2011. Old and new plasma biomarkers in HIV-1 infected African-American women. AIDS (Editorial Comment), in press.

Project Title:
Macrophage polarization and human immunodeficiency virus (HIV) infection
Background and rationale
Mononuclear phagocytes are an important target of HIV infection and replication.
However, the potential role of cytokine-directed polarization into either proinflammatory
(M1) or anti-inflammatory (M2) macrophages has not been
thoroughly investigated in the context of this viral disease. We have already
defined the fundamental features of human M1 and M2 macrophages by exposing
conventional monocyte-derived macrophages (MDM) to either tumor necrosis
factor-a plus interferon-g (M1) or interleukin-4 (IL-4; M2) in terms of differential
expression and modulation of cell surface determinants as well as of secretion of
chemokines and cytokines that may play a relevant role in HIV infection. Of
interest, both M1 and M2 polarization resulted in a transient decrease of CCR5-
dependent (R5) HIV-1 replication in comparison to control unpolarized autologous
MDM, an inhibitory pattern supported, at least in part, by a transient
downregulation of CD4, the primary viral receptor for entry, in contrast to the
viral co-receptor CCR5 that is not decreased in M1-MDM and it is even
upregulated under M2-polarizing conditions at the time of infection. Kinetic
analyses indicated that M1 polarization induces a stronger but less durable
inhibitory effect on HIV-1 replication compared to M2 conditioning. M1-MDM show
an increased secretion of the CCR5-binding chemokine CCL3 as well as of CXCL10
and IL-6. Conversely, M2-MDM are characterized by a modest up-regulation of
the HIV inhibitory chemokine CCL22 and of IL-10. Of note, M1 polarization
induces a delayed downregulation of M2-related chemokine and cytokines and
vice versa. These preliminary findings suggest that polarization of tissue
macrophages in either M1 or M2 cells in response to cytokines or bacterial
products may favor a state of latent over productive infection and, therefore,
impair the capacity of the adaptive T cells response to eliminate macrophage viral
Specific goals
While the pro-inflammatory (M1) pathway of differentiation and activation of
macrophages is well characterized, there are different modalities to induce M2
polarization in addition to IL-4, including cell stimulation by IL-10 and Toll-like
receptor ligands whereas, in addition, deactivating factors such as transforming
growth factor-β can also profoundly affect macrophage function. The regulatory
effect of these cytokines on HIV infection and replication has been previously
investigated, but not in the context of macrophage polarization. Furthermore, the
possibility to exploit cell lines, such as promonocytic U937 cells, as inducible
models of M1/M2 polarization will be part of the project. In addition to learn how
to perform experiments under biosafety level-3 (BSL-3) conditions and the basic
fundamentals to study live HIV infections, this project will provide expertise on
the immunology of human macrophages, and on molecular assays related to
characterize viral transcription, protein expression, and living cell imaging.
Key references
E. Cassol, M. Alfano, P. Biswas, & G. Poli. Monocyte-derived macrophages and
myeloid cell lines as targets of HIV-1 replication and persistence. J. Leuk. Biol.
80:1018-1030, 2006.
E. Cassol, C. Rizzi, L. Cassetta, M. Alfano, & G. Poli. M1 and M2a polarization of
human monocyte-derived macrophages inhibits HIV-1 replication by distinct
mechanisms. J. Immunol., 182: 6237-6246, 2009.
E. Cassol, L. Cassetta, C. Rizzi, M. Alfano, & G. Poli. Macrophage polarization and
HIV-1 infection. J. Leuk. Biol., 87:599-608, 2010.

Project Title:
HIV-1 envelope-dependent CCR5 vs. CXCR4 signaling and gene expression in primary CD4+ T lymphocytes
Background and rationale
The definition of the precise modality of HIV infection via interaction with a
primary cell surface receptor (CD4) and chemokine co-receptor (CCR5 or CXCR4)
has allowed to characterize both the relevance of these two co-receptors in interindividual
viral transmission (both horizontal, sexual or blood-related, and
vertical, i.e. mother-to-child) and in the world pandemics. It is very clear that
both events are driven mostly, if not exclusively, by usage of CCR5 (R5 virus)
whereas the utilization of CXCR4 occurs only during the late stages of HIV disease
and it is usually associated with the maintenance of CCR5 use (so called
dualtropic R5X4 strains). Thus, R5 viruses have an evolutionary advantage vs.
CXCR4-using viruses in terms of efficiency of transmission and spreading in the
general population. In this regard, we have early described a model system based
on the suboptimal stimulation of cord blood derived primary cell lines in which R5
viruses efficiently replicate while X4 do not unless re-stimulated by T cell
activating signals (E. Vicenzi et al., J. Virol. 1999).
Based on this system, we have defined a transcriptome of about 2,000
genes either commonly or differentially regulated by molecularly isogenic HIV-1
clones differing only for their chemokine co-receptor use (CCR5 or CXCR4).
Specific goals
In order to investigate which genes were differentially affected by isogenic
R5 and X4 HIV-1 by a microarray approach we have recently introduced a restimulation
step with anti-CD3 + anti-CD28 mAbs and confirmed the previously
described pattern of R5-skewed replication.
In addition, in collaboration with Prof. Alessandro Aiuti (TIGET) we have
recently reproduced a similarly discordant phenotype based on post-entry
restriction of X4 viruses in peripheral blood leukocytes isolated from children
rather than adults; in the same setting, we have also explored the capacity of
leukocytes isolated from children affected by congenital immunodeficiency either
before and after having received gene therapy-based replacement of their CD34+
cells, with similar results (S.A. Mariani et al., in preparation).
Therefore, the full phenotypic and functional characterization of both the
originally modified and of this second model system will represent the central aim
of the project and will include the comparison of gene expression profiles
determined in the original cord blood based model described above.
Key references
E. Vicenzi, P. Panina-Bordignon, P. Biswas, A. Brambilla, M. Cota, F. Sinigaglia, &
G. Poli. Envelope-dependent restriction of human immunodeficiency virus type 1
spreading in CD4(+) T lymphocytes: R5 but not X4 viruses replicate in the
absence of T-cell receptor restimulation. J. Virol. 73:7515-7523, 1999.
E. Vicenzi, P. Panina-Bordignon, G. Vallanti, P. Di Lucia, & G. Poli. Restricted
replication of primary HIV-1 isolates using both CCR5 and CXCR4 in Th2 but not
in Th1 CD4+ T cells. J. Leuk. Biol., 72:913-920, 2002.
S.A. Mariani, E. Vicenzi, & G. Poli. Asymmetric HIV-1 co-receptor use in activated
CD4+ T lymphocytes. J. Transl. Res., 2010, in press.