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

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Study Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT01895920
Study type	Interventional
Source	French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Contact
Status	Completed
Phase	N/A
Start date	January 2013
Completion date	February 2018

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Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

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

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms