Torque Teno Virus A novel biomarker for the analysis of immune - - PowerPoint PPT Presentation

Torque Teno Virus

A novel biomarker for the analysis of immune competence in HIV infection?

André Fuchs and Livia Schmidt Department of Gastroenterology, Hepatology and Infectious Diseases (Direktor Prof. Dr. D. Häussinger) Institute of Virology (Director Prof. Dr. J. Timm)

Professor Andrea de Luca † 4 Feb 2019

www.who.int/hiv

Torque Teno Virus

• Formerly known as "Transfusion Transmitted Virus"; first

description 1997

• Single stranded, uncoated DNA virus
• Group of anelloviruses that make up a large proportion of the

human virome

• No clinical manifestations known in humans
• High prevalence in the normal population with infection rates
• f >90%; infection shortly after birth
• The (healthy) human immune system holds back virus

replication but is not able to suppress the virus permanently

• TTV plasma concentration increases with age (senescence of

the immune system)

www.lickr.com

https://viralzone.expasy.org/772

TTV as a marker of immune function

Suggested as a marker for immune function:

– Patients with immunosuppression after solid organ transplantation (e.g. lung, kidney, liver)

(Görzer et al., 2015; Schiemann et al., 2017; Kazemi et al., 2015)

– In patients after allogeneic haematopoietic stem cell transplantation

(Gilles et al., 2017; Albert et al., 2018)

 Helpful in assessing the risk of

• pportunistic infections and organ

rejection due to formation of antibodies

TTV as a marker of immune function

Suggested as a marker for immune function:

– Patients with immunosuppression after solid organ transplantation (e.g. lung, kidney, liver)

(Görzer et al., 2015; Schiemann et al., 2017; Kazemi et al., 2015)

– In patients after allogeneic haematopoietic stem cell transplantation

(Gilles et al., 2017; Albert et al., 2018)

 Helpful in assessing the risk of

• pportunistic infections and organ

rejection due to formation of antibodies TTV and HIV-Infection:

(Shibayama et al., 2001; García-Álvarez et al., 2012)

 HIV-infected patients:

− On average, have a higher plasma concentration

• f TTV

− Plasma concentration of TTV and CD4 cell count are inversely correlated

HIV and immunodeficiency

Thomas Splettstoesser, www.scistyle.com

฀ Decrease in CD4 cell count and progressive immunodeficiency during chronic HIV infection ฀ Increasing probability of opportunistic infections and

• ther AIDS-defining diseases

But:

• Progress of CD4 cell loss and speed of immune

reconstitution after initiation of ART individually different

• Patienten Patients with AIDS-defining diseases without

significantly limited CD4 cell count (> 200/µl)

• So-called elite controllers
• Immune Reconstitution Inflammatory Syndrome (IRIS)

HIV and immunodeficiency

Thomas Splettstoesser, www.scistyle.com

฀ Decrease in CD4 cell count and progressive immunodeficiency during chronic HIV infection ฀ Increasing probability of opportunistic infections and

• ther AIDS-defining diseases

But:

• Progress of CD4 cell loss and speed of immune

reconstitution after initiation of ART individually different

• Patienten Patients with AIDS-defining diseases without

significantly limited CD4 cell count (> 200/µl)

• So-called elite controllers
• Immune Reconstitution Inflammatory Syndrome (IRIS)

TTV as biomarker in HIV infection

The plasma TTV DNA values in HIV-1 infected patients correlate with the risk of AIDS events and predict the degree of immune regeneration after initiation of antiretroviral therapy.

TTV as biomarker in HIV infection

The plasma TTV DNA values in HIV-1 infected patients correlate with the risk of AIDS events and predict the degree of immune regeneration after initiation of antiretroviral therapy.

Evaluation of TTV as a functional biomarker for immune competence in chronically HIV-infected patients

TTV as biomarker in HIV infection

• Project 1: Correlation of TTV with HIV plasma

concentration and CD4 cell count in RESINA cohort patients

• Project 2: Evaluation of TTV plasma

concentration as a predictor of regeneration

• d immune function
• Project 3: Case-control study to compare

matched patients with AIDS event versus patients without AIDS event

• Projects in planning and preparation

Projects in detail

• Project 1
• Project 2
• Project 3
• Planned

projects

Correlation of TTV with HIV plasma concentration and CD4 cell count in RESINA cohort patients

– Retrospective Analysis of TTV Plasma Concentrations in ART-naive HIV Patients – Analyses within two groups (CD4 > 200 /µl vs. ≤ 200 /µl) at two different time points

Projects in detail

1,00E+00 1,00E+02 1,00E+04 1,00E+06 1,00E+08 1,00E+10 1,00E+12 1,00 100,00 10000,00 1000000,00 100000000,00

TTV plasmaconcentration (cop/ml, Log) HIV plasmaconcentration (cop/ml, Log)

Y-Werte Baseline Data

• Project 1
• Project 2
• Project 3
• Planned

projects

Projects in detail

1,00E+00 1,00E+02 1,00E+04 1,00E+06 1,00E+08 1,00E+10 1,00E+12 0,00 0,10 0,20 0,30 0,40 0,50 0,60 0,70 0,80 0,90 1,00

TTV plasmaconcentration (cop/ml, Log) CD4 cell count (x103/µl)

Y-Werte Baseline data

• Project 1
• Project 2
• Project 3
• Planned

projects

Projects in detail

Evaluation of TTV plasma concentration as a predictor of immune system regeneration

• Project 1
• Project 2
• Project 3
• Planned

projects