We propose to demonstrate that HIV-1 and SARS-CoV-2 are capable of targeting long-livedHSPC 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.
Inclusion Criteria:
HIV patients :
- HIV-positive patients with a negative or positive viral load.
- managed at Ambroise Paré Hospital.
- patients with a bone marrow biopsy or myelogram performed as part of their care.
Healthy subjects without HIV - patients with a BM biopsy or myelogram performed as part
of their care for a suspected hematological pathology.
Management at Ambroise Paré Hospital.
Exclusion Criteria:
-
Hematology and interne medicine department, Ambroise Paré hospital - APHP
Boulogne-Billancourt, France
Claude CAPRON, MD, PhD
+ 33 01 49 09 58 47
claude.capron@aphp.fr
Fernando REAL, PhD
+ 33 03 20 87 12 01
fernando.real@cnrs.fr