Immunology, Transplantation and Infectious diseases
The Unit performs translational research on HIV Infection of the Central Nervous System, Progressive Multifocal Leukoencephalopathy (viral and host/immune determinants of disease) and other HIV-associated complications affecting the CNS.
Neurovirology Unit has three main research projects:
- The Central Nervous System (CNS) as a reservoir for HIV. The group is characterizing cases of cerebrospinal fluid (CSF)-escape, both phenotypically (clinically, by neuroimaging), virologically (molecular analysis of CSF virus variants) and by immuneactivation and neuronal damage biomarkers. The relevance of such studies is in the perspective of HIV eradication, which is currently unfeasible due to virus persistence in cell reservoirs (lymphocytes, macrophages), which reside in certain tissues, such as lymphatic tissues and the CNS itself.
- PML (Progressive Multifocal Leukoencephalopathy), a progressive demyelinating disease that affects immunocompromised people and persons receiving certain 'biological' drugs. The unit has previously contributed to dimostrate that PML is caused by variants of the JC virus (JCV), upon selection of mutations on its external capside protein, and are currently assessing the antibody- and cell-mediated immune responses to both wild-type and mutated JCV. In particular researchers are studying the hypothesis that viral escape from the immunological control may play a key role in the development and progression of PML. Such studies might lead to the identification of patients at risk to develop PML and to a better definition of the immune control mechanisms, which might be exploited to prevent or treat the disease.
- A more recent research area involves the role of physical activity to improve chronic immune activation in HIV-infected persons and thus help improve metabolic markers and reduce the risk of chronic diseases. Group researchers are actively working with the design and application of training protocols supported by the use of smartphone applications and online social groups, to favor and improve adherence to the training programs towards results optimization.
Ferretti F, Bestetti A, Yiannoutsos CT, Musick BS, Gerevini S, Passeri L, Bossolasco S, Boschini A, Franciotta D, Lazzarin A, Cinque P. Diagnostic and prognostic value of JC virus DNA in plasma in Progressive Multifocal Leukoencephalopathy. Clin Infect Dis. 2018 Jan 15. doi: 10.1093/cid/ciy030. [Epub ahead of print]
Bonato M, Galli L, Passeri L, Longo V, Pavei G, Bossolasco S, Bertocchi C, Cernuschi M, Balconi G, Merati G, Lazzarin A, La Torre A, Cinque P. A pilot study of brisk walking in sedentary combination antiretroviral treatement (cART)- treated patients: benefit on soluble and cell inflammatory markers. BMC Infect Dis. 2017 Jan 11;17(1):61.
Joseph J, Cinque P, Colosi D, Dravid A, Ene L, Fox H, Gabuzda D, Gisslen M, Beth Joseph S, Letendre S, Mukerji SS, Nath A, Perez-Valero I, Persaud D, Price RW, Rao VR, Sacktor N, Swanstrom R, Winston A, Wojna V, Wright E, Spudich S. Highlights of the Global HIV-1 CSF Escape Consortium Meeting, 9 June 2016, Bethesda, MD, USA. J Virus Erad. 2016 Oct 5;2(4):243-250.
Ray U, Cinque P, Gerevini S, Longo V, Lazzarin A, Schippling S, Martin R, Buck CB, Pastrana DV. JC polyomavirus mutants escape antibody-mediated neutralization. Sci Transl Med. 2015 Sep 23;7(306):306ra151.
Gorelik L, Reid C, Testa M, Brickelmaier M, Bossolasco S, Pazzi A, Bestetti A, Carmillo P, Wilson E, McAuliffe M, Tonkin C, Carulli JP, Lugovskoy A, Lazzarin A, Sunyaev S, Simon K, Cinque P. Progressive multifocal leukoencephalopathy (PML) development is associated with mutations in JC virus capsid protein VP1 that change its receptor specificity. J Infect Dis. 2011 Jul 1;204(1):103-14.
Cinque P, Koralnik IJ, Gerevini S, Miro JM, Price RW. Progressive multifocal leukoencephalopathy in HIV-1 infection. Lancet Infect Dis. 2009 Oct;9(10):625-3.
Bossolasco S1, Calori G, Moretti F, Boschini A, Bertelli D, Mena M, Gerevini S, Bestetti A, Pedale R, Sala S, Sala S, Lazzarin A, Cinque P. Prognostic significance of JC virus DNA levels in cerebrospinal fluid of patients with HIV-associated progressive multifocal leukoencephalopathy. Clinical Infectious Diseases 2005;40 (5):738-744.
Cinque P1, Nebuloni M, Santovito ML, Price RW, Gisslen M, Hagberg L, Bestetti A, Vago G, Lazzarin A, Blasi F, Sidenius N. The urokinase receptor is overexpressed in the AIDS dementia complex and other neurological manifestations. Ann Neurol. 2004;55(5):687-9.
Cinque P1, Vago L, Mengozzi M, Torri V, Ceresa D, Vicenzi E, Transidico P, Vagani A, Sozzani S, Mantovani A, Lazzarin A, Poli G. Elevated cerebrospinal fluid levels of monocyte chemotactic protein-1 correlate with HIV-1 encephalitis and local viral replication. AIDS 1998;12 (11):1327-1332.
Cinque P1, Vago L, Dahl H, Brytting M, Terreni MR, Fornara C, Racca S, Castagna A, Monforte AD, Wahren B, Lazzarin A, Linde A. Polymerase chain reaction on cerebrospinal fluid for diagnosis of virus-associated opportunistic diseases of the central nervous system in HIV-infected patients. AIDS 1996;10 (9):951-958.
Cinque P, Brytting M, Vago L, Castagna A, Parravicini C, Zanchetta N, D'Arminio Monforte A, Wahren B, Lazzarin A, Linde A. Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 1993 Aug 14;342(8868):398-401.