This Research Group represents the evolution of the former “AIDS Immunopathogenesis Unit” (1994-2020). Central focus will be the investigation of the role of human monocytes and macrophages in HIV/AIDS and other viral infections, including Zika virus and SARS-CoV-2/COVID-19.
This research group will continue to pursue the investigation on the role of human monocytes and macrophages as potential HIV reservoirs both in the presence and absence of combination antiretroviral therapy (cART). The persistence of a relatively small pool of persistently infected cells in spite of cART is indeed considered the main obstacle to viral eradication thereby rendering the infection a chronic disease with increased comorbidities with a heavy burden both for the individual and the public health systems. While the key phenotypic and molecular features of the proviral reservoir in CD4+ T cells have been well defined, much less is known on the contribution of myeloid cells to the overall viral load. In this regard, we have optimized an in vitro model based on pro-inflammatory (M1) functional polarization of primary human monocyte-derived macrophages (MDM) to study the specific features of the HIV reservoir in these cells, including their peculiarity of storing infectious virions in subcellular compartments named “Virus Containing Compartments (VCC). We will also exploit this model for searching candidate pharmacological agents capable of perturbing the macrophage-associated HIV reservoirs either in terms of “shock and kill” or “block and lock” strategies.
A second goal will be the investigation of the role of role of human monocytes and macrophages in other viral infections, currently focusing on Zika virus (ZIKV) and human pathogenic coronaviruses, i.e. SARS-CoV-1 and SARS-CoV-2, in close collaboration with the Viral Pathogenesis and Biosafety Research Group headed by Elisa Vicenzi. As for HIV-1, we have already substantial evidence that human MDM sustain productive ZIKV infection whereas M1-polarized MDM restrict its replication. Concerning human pathogenic coronaviruses, as human MDM express their entry receptor ACE-2, we are investigating their susceptibility as targets of either productive or restricted infection in comparison to epithelial cells of the respiratory tract.
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F. Graziano, M. Desdouits, L. Garzetti, P. Podini, M. Alfano, A. Rubartelli, R. Furlan, P. Benaroch & G. Poli. Extracellular ATP induces the rapid release of HIV-1 from virus containing compartments of human macrophages. Proc. Natl. Acad. Sci. (USA), 112:E3265-73, 2015.
F. Graziano, E. Vicenzi, & G. Poli. Immuno-pharmacological Targeting of Virus Containing Compartments in HIV-1 Infected Macrophages. Trends in Microbiology, 24:558-567, 2016.
E. Saba, P. Panina-Bordignon, I. Pagani, M. Origoni, M. Candiani, C. Doglioni, G. Taccagni, S. Ghezzi, J. Alcami, E. Vicenzi & G. Poli. 5-Hydroxytyrosol inhibits HIV-1 replication in primary cells of the lower and upper female reproductive tract. Antiviral Research, 142:16-20, 2017.
I. Pagani, S. Ghezzi, A. Ulisse, A. Rubio, F. Turrini, E. Garavaglia, M. Candiani, C. Castilletti, G. Ippolito, G. Poli, V. Broccoli, P. Panina-Bordignon & E. Vicenzi. Human endometrial stromal cells are highly permissive to productive infection by Zika virus. Scientific Reports, 7:44286, 2017.
F. Graziano, G. Aimola, G. Forlani, F. Turrini, R.S. Accolla, E. Vicenzi & G. Poli. Reversible Human Immunodeficiency Virus Type-1 latency in primary human monocyte-derived macrophages induced by sustained M1 polarization. Scientific Reports, 8:14249, 2018.
F. Graziano, E. Vicenzi & G. Poli. The ATP/P2X7 Axis in Human Immunodeficiency Virus infection of Macrophages. Current Opinion in Pharmacology, 47:46-52, 2019.
C.K. Psomas, K. Salzwedel, M. Stevenson, G. Poli, J.P. Routy, D. Margolis, N. Chomont, & A. Lafeuillade. Highlights of the 9th edition of the Conference on HIV Persistence During Therapy, 10-13 December 2019, Miami, Florida, USA. J. Virus Erad., 6:85-89, 2020.
I. Pagani, G. Poli & E. Vicenzi, TRIM22. A multitasking antiviral factor. Cells, 10:1864, 2021.
I. Pagani, P. Demela, S. Ghezzi, E. Vicenzi, M. Pizzato & G. Poli. Host restriction factors modulating HIV latency and replication in macrophages. Int. J. Mol. Sci., 23:3021, 2022.
Fabio Romerio, Elisa Vicenzi & Guido Poli, Editors. “HIV Reservoirs: Modeling, Quantification, and Approaches to a Cure” – Springer Protocols, Humana Press, 2021.