Immunology, Transplantation and Infectious diseases

Viral pathogens and biosafety

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Head of Unit

Elisa Vicenzi

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The focus of this research Unit has always been the study of human viral pathogens with the ultimate goal of contributing to prevention and treatment of their related diseases. In particular, the group has focused on TRIM22, an E3- ubiquitin ligase induced by type I interferon, that restricts influenza A virus by promoting ubiquitination and degradation of the viral nucleoprotein. More recently, the unit has oriented its research towards the spread of Zika virus. In 2015 the neurotropic Zika virus (ZIKV) surfaced in Brazil with compelling evidence linking the infection to an outbreak of microcephaly in newborns. Taking advantage of the IRCCS Ospedale San Raffaele multidisciplinary research expertise, the group investigated the pathogenesis of ZIKV infection by studying its tropism for cells of the female genital tract.

Research activity

Viral pathogens and bionafety Unit discovered that TRIM22 restriction of influenza virus is likely acquired by a selection force that involves the cytotoxic T lymphocyte response. The group had earlier reported that TRIM22 restricts HIV-1 replication, albeit by an E3-independent mechanism, i.e. via inhibition of proviral transcription. Indeed, it is believed that TRIM22 or its interactors could be exploited in therapeutic strategies of “Shock and Kill” aiming at purging the HIV reservoir or “Lock of HIV transcription” in order to permanently silence it.

Moreover, the unit has demonstrated that ZIKV productively infects human endometrial stromal cells particularly in condition of decidualization, a physiological condition induced by progesterone during the secretory phase of the menstrual cycle. Regarding therapeutic approaches for ZIKV infection, for which there are no specific agents, this group found serendipitously that heparin decouples ZIKV replication from virus-induced cell death, an effect that group researchers are currently investigating in greater detail.