HIV-1, SARS-CoV-2
Conditions
Keywords
HIV-1, SARS-CoV-2, Hematopoietic Progenitors, Virus-induced, Immunosuppression
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate if infected HSPC would modulate the bone marrow environment | at 1 year | Evaluate whether these infected HSPC would modulate the bone marrow environment by upregulating inflammatory cytokines detrimental to lymphopoiesis. |
Countries
France
Contacts
Primary ContactClaude CAPRON, MD, PhD
Backup ContactFernando REAL, PhD
Outcome results
None listed