SARS-CoV-2 Clinical Trial
Official title:
Virus-induced Immunosuppression Via Infection of Hematopoietic Progenitors
We propose to demonstrate that HIV-1 and SARS-CoV-2 are capable of targeting long-lived HSPC with self-renewal capacities. These progenitors, thus transformed into host cells, can give rise to a durable source of infected cells with an impact on hematopoiesis.
Virus-induced immunosuppression is the transient or persistent decline of immune cell counts and/or function caused by a virus, favouring its persistence in the host organisms. When sustained, triggered by acute viral replication or maintained by chronic viral infections, virus-induced immunosuppression is a life-threatening condition. It is notoriously observed in chronic HIV-1 infection and even in a considerable fraction of antiretroviral-treated HIV-infected individuals. It is also observed in some individuals recovering from severe and mild-to-moderate COVID-19. Its mechanisms are elusive and efficient therapeutic options are not available. Virus-induced immunosuppression may occur in the periphery (affecting circulating immune cells) or in the bone marrow, affecting hematopoietic stem and progenitor cells (HSPC) and hematopoiesis. Several viruses can infect HSPCs. HIV-1 can directly infect HSC, negatively impacting HSC function and the whole stem cell environment of the bone marrow. Whether HSC can be productively infected by SARS-CoV-2 or just targeted and modulated by it remains uncertain and further studies are required to determine HSPC susceptibility or viral sensing for SARS-CoV-2. Therefore, we will i) Evaluate which hematopoietic stem and progenitor cells (HSPC) are targeted by HIV-1 (in vivo and ex vivo) and SARS-CoV-2 (ex vivo); ii) Evaluate whether these infected HSPC would modulate the bone marrow environment by upregulating inflammatory cytokines detrimental to lymphopoiesis. ;
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