INFECTIOUS DISEASES / Virology
Virology, SARS-CoV-2, COVID-19, HIV-1, AIDS, tick-borne encephalitis, dengue, zika, arbovirus, innate immunity, stress response, virus-host interaction, microscopy, fluorescence, antivirals, diagnostics, surveillance, point-of-care testing
Description of Research
The main focus of our laboratory is the molecular and cell biology of virus-host interactions. We had a long-standing interest in HIV-1 transcriptional and post-transcriptional nuclear regulation, which shifted towards artropod-borne RNA viruses of increasing concern such as tick-borne encephalitis, dengue, west Nile and Zika.
Since the beginning of the COVID-19 epidemic the laboratory has been in the frontline to tackle SARS-CoV-2. To this end, we developed a platform of tools for the study of the virus-host crosstalk: from single protein-protein interactions to the dynamics of host and viral components. Activities included the formulation of protocols for SARS-CoV-2 molecular and serological diagnostics, and the production of on-line tutorials and reagents to enable the development of low-cost in-house assays. SARS-CoV-2 viruses circulating in several countries were sequenced for the first time, and the data was made available to the scientific community. A pipeline for testing antivirals against SARS-CoV-2 was set up, allowing the identification of novel drug candidates.
We are also interested in implementing viral diagnostics for developing countries by technically supporting local scientists and by developing point-of-care portable devices in collaboration with industrial partners. Finally, small molecules derived from screenings, repurposing or rational design are tested for antiviral activity.
The laboratory is taking care of the following core facilities of the ICGEB:
- The Biosafety Level 3 (BSL3) containment facility for the manipulation of pathogenic viruses
- The Fluorescence Microscopy Core Facility
The laboratory actively promotes:
- The ICGEB Workshop on Human RNA Viruses, which takes place every two years in ICGEB Member States (Trieste, 2008; New Delhi, 2010; Buenos Aires, 2012; Istanbul, 2014; Costa Rica 2016, Shanghai 2018)
- The ICGEB Practical Course on Fluorescence Microscopy (Trieste, 2016; Trieste 2017; Trieste 2018; New Delhi 2019/2021)
- The ICGEB COVID-19/SARS/CoV-2 Resources platform (link: https://www.icgeb.org/covid19-resources/), Twitter and Instagram (@marcello_lab)
The Group contributed to SARS-CoV-2 genomic surveillance in ICGEB Member States (Paulino-Ramirez et al., Microbiol Resour Announc 1021; Bitew et al; Microbiol Resour Announc et al., 2022;.. Giovanetti et al., Commun Biol 2021) and made important steps in the development of diagnostic tools, contributing to the deployment of RT LAMP in Africa (Baba et al, EClinicalMedicine, 2021; Lombardo, Covid 2021).
Marcello A, Civra A, Milan Bonotto R, Nascimento Alves L, Rajasekharan S, Giacobone C, Caccia C, Cavalli R, Adami M, Brambilla P, Lembo D, Poli G, Leoni V. The cholesterol metabolite 27-hydroxycholesterol inhibits SARS-CoV-2 and is markedly decreased in COVID-19 patients. Redox Biol. 2020 Aug 10; 36:101682. doi: 10.1016/j.redox.2020.101682
Licastro D, Rajasekharan S, Dal Monego S, Segat L, D’Agaro P, Marcello A and the FVG Laboratory Group on COVID-19. Isolation and full-length genome characterization of SARS-CoV-2 from COVID-19 cases in Northern Italy. J Virol. 2020 May 18; 94 (11): e00543-20. doi: 10.1128/JVI.00543-20
Caracciolo I, Mora Cardenas E, Aloise C, Carletti T, Segat L, Burali MS, Chiarvesio A, Totis V, Avšič – Županc T, Mastrsangelo E, Manfroni G, D’Agaro P and Marcello A. Comprehensive response to Usutu virus following first isolation in blood donors in the Friuli Venezia Giulia Region of Italy: development of recombinant NS1-based serology and sensitivity to antiviral drugs. PLoS Negl Trop Dis. 2020 Mar 30; 14 (3): e0008156. doi: 10.1371/journal.pntd.0008156.
Mora-Cárdenas E, Aloise C, Faoro V, Knap Gašper N, Korva M, Caracciolo I, D’Agaro P, Avšič-Županc T, Marcello A. Comparative specificity and sensitivity of NS1-based serological assays for the detection of flavivirus immune response.PLoS Negl Trop Dis. 2020 Jan 29; 14 (1): e0008039. doi: 10.1371/journal.pntd.0008039
Carletti T, Zakaria MK, Faoro V, Reale L, Kazungu Y, Licastro D, Marcello A. Viral priming of cell intrinsic innate antiviral signaling by the unfolded protein response. (2019) Nat Commun ;10(1):3889. doi: 10.1038/s41467-019-11663-2
Sarracino A, Gharu L, Kula A, Pasternak AO, Avettand-Fenoel V, Rouzioux C, Bardina M, De Wit S, Benkirane M, Berkhout B, Van Lint C, Marcello A. Posttranscriptional Regulation of HIV-1 Gene Expression during Replication and Reactivation from Latency by Nuclear Matrix Protein MATR3. Mbio (2018) Nov 13;9(6). pii: e02158-18. doi: 10.1128/mBio.02158-18.