HIV Infection
Conditions
Keywords
HIV, Biofilm, Transmission
Brief summary
This project aims at characterizing HIV-1 viral biofilms structural and functional properties and at deciphering its role as a new viral reservoir and as a new mode of viral spread. The prospective national study will be conducted on cells isolated from blood samples from 20 patients infected with HIV.
Detailed description
The investigators' preliminary data indicate that besides free infectious viral particles, HIV-1 infected cluster of differentiation 4 (CD4+) lymphocytes also produce extracellular viral assemblies wrapped in an extracellular matrix cocoon and tightly bound to the surface of the cell. Importantly, these structures are infectious, transferred to target cells upon intercellular contacts and they are key role in HIV-1 spread between T lymphocytes. HIV-1 viral biofilm could be important not only for direct transmission of the virions but also for trans-infection , a process our objectives are: * to better characterize the molecular composition and the architecture of this biofilm (using proteomics, glycomic superresolution cell imaging approaches) with regard to its properties (infectivity, adhesiveness, protection of virions) and to determine whether cells from infected patients produce such structures. * to delineate the viral factors regulating the formation of these new infectious structures (with a particular attention on Tat, Vpu and Nef HIV-1 encoded using mutant viruses or expression vectors). * to investigate the lymphocyte pathways regulating the viral biofilms formation and composition in extracellular matrix (ECM) proteins (using quantitative polymerase chain reaction (qPCR) and siRNA). * to determine whether those viral biofilms are involved in HIV-1 transmission by transinfection * to study the contribution of those infectious structures and the dynamics of their transmission in lymph nodes. This project may contribute to decipher the role of viral biofilms in HIV-1 transmission. Ultimately, we intend to determine how the interference of retroviral infections with T cell activation pathways modulates the pattern of ECM production by T cells, tuning viral biofilm composition and regulating viral dissemination.
Interventions
OTHERBlood sample
Sponsors
ANRS, Emerging Infectious Diseases
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * able to give written consent * HIV positive serology HIV1 * Viral load \> 10 000 copies/ml * CD4 T cells \> 100 cells/mm3 * or Treated by antiretroviral therapy (ARV) for less than 6 months * Covered by French Social Security
Exclusion criteria
* Involved in a clinical trial * Pregnancy (inclusion can be postponed) * No covered by French Social Security
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The percentage of HIV positive patients with cells producing biofilms. | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| The number of cells with biofilms identified among the HIV positive patients presenting such structures. | 2 years |
Countries
France
Outcome results
None listed