Project Structure


To achieve project objectives PathCo project is organized in 7 Work Packages (WPs):


WP1: Define the genetic and molecular basis for Mycobacterium tuberculosis (Mtb) regulation of HIV-1 replication

The aim of this work package is to determine the effect divergent Mtb cell wall constituents play in modulating HIV-1 infection in a variety of cell types. From the DNA full-genome sequence analysis of a large number of Mtb isolates from HIV-1/Mtb co-infected patients sequence variations will be correlated to disease. Using standard molecular techniques genes will either be introduced or knocked-down from appropriate strains of Mtb for testing. These strains will be studied in vitro for their effect(s) on innate immune responses and HIV-1 replication.


WP2: The role of HIV-1 infection and associated inflammation in HCV replication

The objective of WP2 is to increase our understanding of the interactions between HIV-1 and HCV. A number of in vitro assays will be developed to allow studies on viral interactions in co-culture systems with different cell types including: lymphocytes, DCs, hepatocytes and sinusoidal endothelial cells and tissue explant models. We will develop new reporter viruses that will enable rapid and efficient identification of infected cell types. Furthermore, we will generate and evaluate the ability of two host glycoproteins, BSSL and MUC6, and their derived peptides to bind DCs and block viral trans-infection.


WP3: To identify common pathways for Malaria and HCV entry into hepatocytes and to discover novel inhibitors

The objective of WP3 is to evaluate common pathways of Plasmodium and HCV entry into hepatocytes with the goal to identify inhibitors that will block infection of both pathogens. In addition, co-infection studies with liver cell culture systems developed in WP2 will identify the effect(s) of both pathogens alone and in combination on immune cell activation.


WP4: To generate a humanized mouse model system that supports pathogen co-infection

The aim of this work package is to generate humanized mouse model systems that support pathogen co-infection(s). Our priority is to generate a mouse with a reconstituted humanized immune system and a chimeric liver expressing human hepatocytes. Such a model will provide a means to study pathogen interactions be it HIV-1/HCV or HIV-1/malaria and associated pathologies. By dual-infecting the mice with both pathogens and the utilizing novel viral tools we can assess the significance of one infection on the other and in different anatomical compartments of the mice.


WP5: To identify the effect(s) of HIV-1 infection on HCV specific host immune responses

The objective of WP5 is to utilize a number of existing cohorts to address which T- and B-cells as well as DC immune responses are modulated in mono- or HIV-1/HCV co-infected individuals. Using samples from selected individuals we will assay for an array of variant responses and correlate with disease severity for either virus. We will also determine which phenotype of CD4 cells are infected with HIV-1 in HIV-1/HCV co-infected individuals where HCV responses are detected.


WP6: Management, Review and Assessment

The aim of this work package is to guarantee full synergy and integration among PathCo beneficiaries to provide added European value and to extend the state of the art in research on pathogen co-infection and to facilitate the following outcomes:

  • - To reach stated milestones and deliverables
  • - To achieve planned objectives
  • - To recognize problems, to evaluate and adopt actions to solve them.

WP7: Dissemination and Training of PathCo Personnel

The general objective of this work package is to disseminate results as well as general awareness of issues addressed by the PathCo project amongst partners and the wider scientific community.
Particular attention is devoted to ensure an efficient use of the resources to train young scientists to encourage their active participation in research activities and professional development.


Main relationship amongst PathCo WPs


project structure


Beneficiary

Main involvement and contribution to the project

11 - UOL

Overall project coordination. UOL will scientifically be associated with research in WP2 as well as being instrumental in other WPs through generating novel viral tools or immunological analysis (WP1, 4 and 5) and is project leader of WP4.

02 - BHAM

BHAM includes WP1 and WP2 leaders that will: (a) Identify the genetic loci defining Mtb regulation of HIV-1 replication; (b) Establish in vitro cell culture systems that support HIV-HCV co-infection to study the effect(s) of HIV-1 on immune cell capture and dissemination of HCV, immune cell innate signaling and viral specific cellular immune responses; (c) Study common entry pathways of Plasmodium/HCV entry into hepatocytes and evaluate the efficacy of anti-HCV entry inhibitors to block HCV Plasmodia invasion in WP3.  (d) Study HCV infection in murine models in WP4; and   (e) Study neutralizing antibody responses in mono and co-infected subjects and perform statistical analysis of immunological characterization of clinical material in WP5.

03 - INSERM

This beneficiary will be WP3 leader and will be in charge of all Plasmodium studies within the Plasmodium/HCV co-infection program, i.e. ex vivo with human hepatocytes and P. falciparum, in vitro with human hepatoma cells and Plasmodium rodent species and in vivo with P. falciparum and humanized mice models.

04 - UKL-FR

UKL-FR will be WP5 leader and organize the immunological work at various sites listed in this work package. Specifically, this beneficiary will address the virus specific T cell responses in mono- and co-infected patients and will study the effect of HCV infection on lymphocyte trafficking in WP2.

05 - UOXF

UoO will identify the effects of HIV-infection on HCV-specific host immune responses in WP5.

06 - ICSTM

This beneficiary will offer expertise in explant tissue culture models to study sexual routes of HCV transmission and the effect of HIV-1 co-infection on HCV dissemination.

08 - UoCT

This beneficiary will be involved in WP1 to delineate the molecular interactions influencing the Mtb regulation of HIV-1 replication.

09 - IP

IP will be responsible for creating and optimizing the humanized mouse models to be used in WP4. Studies involving pathogen co-infection and associated immune responses will be analyzed by this beneficiary, in close collaboration with other members of the consortium.

10 - ALTA

Working in close contact with the Project Coordinator, ALTA’s specific contribution to this project will be 1) support the coordinator in checking the progress of the administrative work; 2) support the coordinator to coordinate the administrative bodies of the different beneficiaries’ institutions; 3) support the coordinator in  the preparation of scientific reports; 4) assist the coordinator in following IPR issues; 5) support the coordinator to develop and implement plans for communication and visibility of the consortium and 6) support the coordinator in organising project meetings.