PATHOGEN CO-INFECTION


HIV-1, Tubercolosis, Malaria

and Hepatitis C virus


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Pathogen Co-infection: HIV-1, Tuberculosis, Malaria and hepatitis C virus

virus

  • Acquired immune deficiency syndrome (AIDS), tuberculosis (TB) and malaria are the primary infectious diseases causing death world wide. TB is responsible for a third to a half of human immunodeficiency virus type 1 (HIV-1)-associated deaths, particularly in sub Saharan Africa and South East Asia. Malaria is widely spread in tropical Africa and accounts for approximately 800,000 deaths every year. In addition to these pathogens, 170 million people are infected with hepatitis C virus (HCV), which may lead to chronic liver disease, liver cirrhosis and hepatocellular carcinoma. Because of shared routes of transmission, HCV co-infection is recognized as a major cause of morbidity and mortality among HIV-1 infected persons.


  • Effective drugs to control these infectious agents are limited and treatment is made even more challenging by the development of drug-resistant pathogens. Importantly, co-infection with one or more of these pathogens limits the efficacy of available drugs. The epidemiological and clinical features of co-infected subjects is well documented, however, there is a paucity of basic scientific studies addressing the molecular interaction(s) between these pathogens. Variant pathogen strains are known to influence infection and disease outcome, however, the underlying mechanism(s) are unknown.


  • PathCo consortium propose that pathogen evasion and dysregulation of host immune responses play a key role in co-infection associated morbidity. We will test this hypothesis by developing in vitro and ex vivo co-infection model systems to study pathogen interactions. The specific objectives of this project are to improve our understanding of pathogen co-infection effect(s) on host innate and adaptive immune responses and to develop new approaches to dissect pathogen interactions: ranging from the genesis of fluorescent labelled viruses to state-of-the-art tissue explant culture systems and novel humanised mouse models. Translational studies of infected subjects will define pathogen-specific effects on host immune responses and consequences for disease progression. It is imperative that such interactions are elucidated before evaluating new prophylactic or therapeutic strategies in co-infected individuals.



  • PathCo Project Focus
  • The PathCo project brings together powerful multidisciplinary technologies that will improve our understanding of the complex interactions between infectious agents and the host immune response that will significantly improve the management of co-infection associated disease.


  • Recent developments in each of the disease disciplines enable the design of model systems that support pathogen co-infection, highlighting the timeliness of PathCo’s mission to study the biological and immunological consequences of co-infection(s).


  • Ultimately such knowledge will be instrumental in the rational design of new therapies and vaccines to control HIV-1, TB, malaria and HCV. In parallel to generating and utilizing new tools to understand the basic biology of pathogen co-interactions the PathCo consortium members will develop novel anti-microbials for translational research.  The PathCo project will identify new targets for therapy and vaccine design, whilst validating known agents for their ability to block pathogen transmission and to target antigen or anti-pathogen components to dendritic cells (DCs).


  • The PathCo consortium consists of ten beneficiaries from five EU countries (Netherlands, UK, France, Germany and Italy) and one beneficiary from non-EU countries (South Africa).


  • PathCo team is a well-balanced team of immunologists, virologists, clinicians, statisticians, epidemiologists with expertise in HIV/AIDS, TB, malaria and hepatitis C infection research and has the most appropriate scientific and technical background as well as the animal models and instrumentation required to fulfill the goals of this project and to succeed in its mission. PathCo beneficiaries will have access to well-characterised established cohorts of co-infected patients from different geographical locations. Given the widespread global nature of the pathogens under study it is imperative that we are not biased in our selection of patients.








Project info

Acronym: PathCo

EC Contribution: € 5.909.690

Duration: 60 months

Starting date: 01/11/2012

Instrument: Collaborative project


Coordinator:

Bill Paxton

The University of Liverpool Department of Clinical Infection, Microbiology and Immunology Institute of Infection and Global Health

The Ronald Ross Building West Derby Street 8 Liverpool L69 7BE United Kingdom




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     eu-flag


This project is supported through Coordination Theme 1 (Health) of the European Community's FP7. Grant agreement number

HEALTH-F3-2012-305578


Last update: 07/12/2017



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PathCo is split into 5 basic research areas encompassing

the following objectives


- To define the genetic and molecular basis underlying

TB regulation of HIV-1 replication

- To define the role of HIV-1infectionand associated

inflammation on HCV replication

- To identify common pathways defining Malaria

and HCV liver tropism

- To generate humanized mouse model systems

that support pathogen co-infections

- To identify the effect(s) of HIV-1 infection on HCV

specific host immune responses



The PathCo project brings together powerful

multidisciplinary technologies that will improve our

understanding of the complex interactions between

infectious agents and the host immune response

that will significantly improve the management of

co-infection associated disease. Recent developments

in each of the disease disciplines enable the design of

model systems that support pathogen co-infection,

highlighting the timeliness of PathCo’s mission to study

the biological and immunological consequences of

co-infection(s).

Ultimately such knowledge will be instrumental in the

rational design of new therapies and vaccines to

control HIV-1, TB, malaria and HCV. In parallel to

generating and utilizing new tools to understand the

basic biology of pathogen co-interactions the PathCo

consortium memberswill develop novel anti-microbials for

translational research. The PathCo project will identify

new targets for therapy and vaccine design, whilst validating known agents for their ability to block pathogen

transmission and to target antigen or anti-pathogen

components to dendritic cells (DCs).

PATHOGEN CO-INFECTION - THE PROBLEM

Acquired immune deficiency (AIDS), tuberculosis (TB)

and malaria are the primary infectious diseases

causing death worldwide. TB is responsible for a third

to a half of human immunodeficiency virus type 1

(HIV-1)-associated deaths, particularly in sub Saharan

Africa and South East Asia. Malaria is widely spread in

tropical Africa and accounts for approximately 800,000

deaths every year. In addition to these pathogens, 170

million people are infected with hepatitis C virus (HCV),

which leads to chronic liver disease. Because of shared

routes of transmission, HCV co-infection is recognized

as a major cause of morbidity and mortality among

HIV-1 infected persons.

The epidemiology and clinical features of co-infected

subjects is well documented, however, there is a paucity

of basic scientific studies addressing the interactions

between these pathogens. There is undoubtedly a

complex interplay between pathogens and the host

immune response.


PATHCO FOCUS AND OUTCOME

PathCo consortium proposes that pathogen evasion

and dysregulation of host immune responses play a

key role in co-infection associated morbidity. Within

this Project will test this hypothesis by developing in

vitro and ex vivo co-infection model systems to study

co-pathogen interactions. The specific objectives of

PathCo are to improve our understanding of pathogen

co-infection effect(s) on host innate and adaptive

immune responses and to develop new approaches to

dissect pathogen interactions: ranging from the genesis

of fluorescent labelled viruses to state-of-the-art tissue

explant culture systems and novel humanised mouse

models. Translational studies of infected subjects will

define pathogen-specific effects on host immune

responses and consequences for disease progression.

It is imperative that such interactions are elucidated

before evaluating new prophylactic or therapeutic

strategies in co-infected individuals.

PATHCO ALLIANCE

The PathCo consortium consists of nine beneficiaries

from four EU different countries (UK, France, Germany

and Italy) and one beneficiary from non-EU countries

(South Africa).

PathCo is a well-balanced team of immunologists,

virologists, clinicians, statisticians, epidemiologists

with expertise in HIV/AIDS, TB, malaria and hepatitis

C infection research and has the most appropriate

scientific and technical background as well as the

animal models and instrumentation required to fulfill

the goals of this project and to succeed in its mission.

PathCo beneficiarieswill have access to well-characterised

established cohorts of co-infected patients from different

geographical locations.


Technology

In vitro

systems

Advanced

Animal

Models

Human

Immunology

HIV

TB

HIV

HCV

HIV

Malaria

TB

regulation of

HIV replication

TB

regulation of

HIV replication

HIV infectioninflammation

in HCV

replication

Generation

humanized

mouse models

for mono- and

co-infection

HIV infection

on HCV

specific host

immune

responses

Common

pathways

of Malaria and

HCV entry into

hepatocytes

infection

Generation

humanized

mouse models

for mono- and

co-infection



PROJECT ORGANIZATION


pathogen

Co-infeCtion:

HIV-1, Tuberculosis,

Malaria and

hepatitis C virus

University of Birmingham

Jane McKeating - Gurdyal Besra

United Kingdom

www.birmingham.ac.uk

institUt nationaL de La santé

et de La reCherChe médiCaLe

Olivier Silvie - France

www.inserm.fr

UniversitaetskLinikUm freiBUrg

Robert Thimme - Germany

www.uniklinik-freiburg.de

University of oxford

Tao Dong - United Kingdom

www.ox.ac.uk

imperiaL CoLLege of sCienCe,

teChnoLogy and mediCine

Carolina Herrera - Xiao-Ning Xu

United Kingdom- www3.imperial.ac.uk

University of Cape toWn

Robert Wilkinson - South Africa

www.uct.ac.za

institUt pasteUr

James Di Santo - France

www.pasteur.fr

aLta riCerCa e sviLUppo

in BioteCnoLogie s.r.L.U.

Riccardo Bertini - Italy

www.altaweb.eu

PATHCO PARTNERS

pathogen Co-infeCtion:

HIV-1, Tuberculosis, Malaria

and hepatitis C virus

Coordinator:

prof William a paxton phd diC

Department of Clinical Infection,

Microbiology and Immunology

Institute of Infection and Global Health

University of Liverpool

216e, Ronald Ross Building

8 West Derby Street

Liverpool L69 7BE

w.a.paxton@liverpool.ac.uk

www.pathco.org

EC Contribution: € 5.909.690

Duration: 60 months

Starting date: 01/11/2012

University of LiverpooL

Bill Paxton - United Kingdom

www.liv.ac.uk


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