Viral evolution and transmission
The knowledge of the pathogenic mechanisms of infection and disease guide the development of intervention and prevention strategies and new HIV vaccine candidates. At this scope the group focuses mainly on models as mother-to-child transmission of HIV and disease progression in children and adults. In specific Viral evolution and transmission Unit determines the pathways of HIV within the intestinal mucosa, which is the site of viral entry, replication and persistence.
Our main research interests are:
1. The mucosa, the main portal of entry of HIV via all routes of transmission, is the site of major immune subversion early after infection. Data indicate that Dendritic cells (DC) are an early target for HIV and may become a source of virus for the surrounding cells affecting in turn innate and adaptive immune responses. Therefore the group studies with sophisticated imaging technology in vitro and ex vivo: i) the molecular mechanism driving the migration of HIV through the intestinal epithelial barrier; ii) the cellular targets in the mucosa, in specific macrophages and DCs, to identify the possible pathways to invade the tissue and disseminate to other organs; iii) the involvement of DCs and their functional properties in mediating adaptive immune responses at mucosal level; and iv) the role of antibodies with different effector functions in changing the pathways of the virus.
2. The antibody response controlling HIV, as the desirable and ultimate immune response induced by an HIV vaccine. The unit focuses its attention on selected models as mother-to-child transmission of HIV-1 or HIV infected patients controlling the disease or the virus, called Elite and Virus controller. Data show that infected children with slow progression of disease and Elite controllers develop neutralizing antibody and ADCC. Therefore the group: i) characterizes the specificity of these antibody responses to identify relevant targets for a vaccine; ii) developes new approaches to test antibody responses; and iii) adoptes the immunological analysis in preclinical (in rabbits and macaques) and clinical vaccines studies to identify predictive signatures for the development and prioritization of new HIV-1 vaccine candidates.
Peptide specificity in the recognition of MHC class I by natural killer cell clones. Malnati MS, Peruzzi M, Parker KC, Biddison WE, Ciccone E, Moretta A, Long EO SCIENCE 1995, 267(5200):1016-8 10.1126/science.7863326
In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Scarlatti, G; Tresoldi, E; Bjorndal, A; Fredriksson, R; Colognesi, C; Deng, HK; Malnati, MS; Plebani, A; Siccardi, AG; Littman, DR; Fenyo, EM; Lusso, P NATURE MEDICINE 1997, 3(11): 1259-65 10.1038/nm1197-1259
A relapsing inflammatory syndrome and active human herpesvirus 8 infection. Dagna, L, Broccolo, F, Paties, CT, Ferrarini, M, Sarmati, L, Praderio, L, Sabbadini, MG, Lusso, P, Malnati, MS. N. Engl. J. Med. 2005; 353(2):156-163 10.1056/NEJMoa042850
A universal real-time PCR assay for the quantification of group-M HIV-1 proviral load. Malnati MS, Scarlatti G, Gatto F, Salvatori F, Cassina G, Rutigliano T, Volpi R, Lusso P NATURE PROTOCOLS 2008, 3 (7): 1240-48 10.1038/nprot.2008.108
International network for comparison of HIV neutralization assays: the NeutNet report II. Heyndrickx, L; Heath, A; Sheik-Khalil, E; Alcami, J; Bongertz, V; Jansson, M; Malnati, M; Montefiori, D; Moog, C; Morris, L; Osmanov, S; Polonis, V; Ramaswamy, M; Sattentau, Q; Tolazzi, M; Schuitemaker, H; Willems, B; Wrin, T; Feny, EM; Scarlatti, G PLoS One: 2012; 7(5): e36438 - 10.1371/journal.pone.0036438
B-cell subset alterations and correlated factors in HIV-1 infection. Pensieroso, S; Galli, L; Nozza, S; Ruffin, N; Castagna, A; Tambussi, G; Hejdeman, B; Misciagna, D; Riva, A; Malnati, M; Chiodi, F and Scarlatti, G AIDS: 2013; 27(8): 1209-1217 – 10.1097/QAD.0b013e32835edc47
R5 HIV-1 envelope attracts dendritic cells to cross the human intestinal epithelium and sample luminal virions via engagement of the CCR5. Cavarelli, M; Foglieni, C; Rescigno, M; Scarlatti, G EMBO Mol. Med.: 2013; 5(5): 776-794 – 10.1002/emmm.201202232
Beneficial effects of cART initiated during primary and chronic HIV-1 infection on immunoglobulin-expression of memory B-cell subsets. Pogliaghi, M and Ripa, M; Pensieroso, S; Tolazzi, M; Chiappetta, S; Nozza, S; Lazzarin, A; Tambussi, G; Scarlatti, G PLoS ONE: 2015; 10(10): e0140435 – 10.1371/journal.pone.0140435
Activating Killer Immunoglobulin Receptors and HLA-C: a successful combination providing HIV-1 control. Malnati MS, Ugolotti E, Monti MC, De Battista D, Vanni I, Bordo D, Sironi F, Larghero P, Di Marco E, Biswas P, Poli G, Vicenzi E, Riva A, Tarkowski M, Tambussi G, Nozza S, Tripodi G, Marras F, De Maria A, Pistorio A, Biassoni R. Sci Rep. 2017; 7:42470 10.1038/srep42470
Interdomain Stabilization Impairs CD4 Binding and Improves Immunogenicity of the HIV-1 Envelope Trimer. Zhang P, Gorman J, Geng H, Liu Q, Lin Y, Tsybovsky Y, Go EP, Dey B, Andine T, Kwon A, Patel M, Gururani D, Uddin F, Guzzo C, Cimbro R, Miao H, McKee K, Chuang GY, Martin L, Sironi F, Malnati MS, Desaire H, Berger EA, Mascola JR, Dolan MA, Kwong PD, Lusso P. Cell Host Microbe. 2018 23(6):832-844 10.1016/j.chom.2018.05.002.
Structure and immunogenicity 1 of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence. Sliepen K, Woo Han B, Bontjer I, Mooij P, Garces F, Behrens A-J, Rantalainen K, Kumar S, Sarkar A, Brouwer P, Hua Y, Tolazzi M, Schermer E, Torres J.L, Ozorowski G, van der Woude P, Torrents de la Peña A, van BreemenM, Camacho-Sánchez MJ, Burger J.A., Medina-Ramírez M, González N, Alcami J, LaBranche C, Scarlatti G, van Gils M.J., Crispin M, Montefiori D.C, Ward A.B, Koopman G, Moore J.P, Shattock R.J, Bogers W.M, Wilson I.A., Sanders R.W. Nat Commun. 2019 May 29;10(1):2355. 10.1038/s41467-019-10262-5
A Novel System to Discriminate HLA-C mir148a Binding Site by Allele-Specific Quantitative PCR. Mauro S Malnati, Priscilla Biswas, Elisabetta Ugolotti, Eddi Di Marco, Francesca Sironi, Francesca Parolini, Lucia Garbarino, Michela Mazzocco, Donato Zipeto, Roberto Biassoni. HLA 2020 96(3):312-322 10.1111/tan.13971
Eliminating postnatal HIV transmission in high incidence areas: need for complementary biomedical interventions. Van de Perre, P and Goga, A; Ngandu, N; Nagot, N; Moodley, D; King, R; Molès, JP; Mosqueira, B; Chirinda, W; Scarlatti, G; Tylleskär, T; Dabis, F and Gray, G Lancet: 2021; 397(10281): 1316-1324 – 10.1016/S0140-6736(21)00570-5
Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival. Dispinseri, S; Secchi, M; Pirillo, MF; Tolazzi, M; Borghi, M; Brigatti, C; De Angelis, ML; Baratella, M; Bazzigaluppi, E; Venturi, G; Sironi, F; Canitano, A; Marzinotto, I; Tresoldi, C; Ciceri, F; Piemonti, L; Negri, D and Cara, A and Lampasona, V and Scarlatti, G Nat Commun: 2021; 12: 2670 – 10.1038/s41467-021-22958-8
Seasonal betacoronavirus antibodies’ expansion post-BNT161b2 vaccination associates with reduced SARS-CoV-2 VoCs neutralization. Dispinseri S *, Marzinotto I*, Brigatti C, Pirillo M, Tolazzi M, Bazzigaluppi E, Canitano A, Borghi M, Gallinaro A, Caccia R, Vercesi R, McKay P, Ciceri F, Piemonti L, Negri D, Cinque P, Cara A, Scarlatti G*, Lampasona V* J Clin Immunol. 2022 Jan 9:1-11. 10.1007/210875-021-01190-5