Viral Biofilms: Hijacking T Cell Extracellular Matrix to Regulate HIV-1 Spread?

Study Overview
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Brief Summary
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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
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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.

Conditions
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HIV Infection

Intervention / Treatment
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* Other: Blood sample


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIV infection<br>20 HIV infected subjects | Other: Blood sample<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of HIV positive patients with cells producing biofilms. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of cells with biofilms identified among the HIV positive patients presenting such structures. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Biofilm, Transmission