Karin Metzner

HIV-1 genomics in vivo

We are interested in the genomic organisation, diversity & evolution of HIV-1 and the subsequent consequences on HIV-1 transmission, maintenance of reservoirs, and pathogenesis.

Our current research projects comprise investigations on (1) the mechanisms of viral escape from the selective pressure of antiretroviral drugs, (2) the evolution of HIV-1 in patients with primary HIV-1 infection, and (3) the impact of HIV-1 integration sites on pathogenesis, and (4) identifying factors underlying latency.

 
 

Group members


 

Projects

HIV-X Deciphering host-virus interactions to cure HIV

Valentina Vongrad, PhD (Post Doc)

In order to develop strategies with which the HIV reservoir can be eliminated, we need first to understand how HIV manages to establish and maintain the latent reservoir. To achieve this ambitious goal, a nationwide and interdisciplinary project, called HIV-X has been started in February 2015. Based on the Swiss HIV Cohort Study, which was initiated in 1988 and covers more than half of all registered HIV-infected individuals in Switzerland, we will study a group of approximately 1,600 HIV-1 infected individuals longitudinally who have been treated successfully with antiretroviral therapy. Our group is measuring the decay rate of the latent reservoir as well as the viral genome sequencing in these individuals using the most modern methods. Besides us, the following research groups are participating: Prof. Huldrych Günthard (UZH/USZ, principal investigator) Prof. Niko Beerenwinkel (ETHZ, SIB), Dr. Jasmina Bogojeska (IBM), Prof. Sebastian Bonhoeffer (ETHZ), Prof. Jacques Fellay (EPFL), Prof. Roger Kouyos (UZH/USZ), Prof. Volker Roth (UniBas). http://www.systemsx.ch/projects/medical-research-and-development-projects/hiv-x/



 

 

 HIV-1 integration sites and their impact on HIV-1 pathogenesis

Yik Lim Kok (Post Doc)

Although an HIV-1 infection can be effectively treated, its cure is impeded by the persistence of the latent HIV-1 reservoir, which is invisible to the host immune surveillance and unsusceptible to antiretroviral therapy. Latent HIV-1 proviruses are transcriptionally silent. This project involves the examination of HIV-1 integration sites in search of factors that govern the transcriptional activity of HIV-1 proviruses.

 

Diversity and evolution of HIV

Nottania Kay Campbell (PhD student)

Primary HIV-1 infection is characteristically established by one or a few founder viruses. In the absence of treatment, the initial homogenous viral swarm goes on to diversify and establish a chronic infection in the patient.

This project focuses on characterizing the genetic landscape of the virus that establishes the initial infection. This is done by sequencing viruses from acutely HIV-1 infected individuals enrolled in the Zurich Primary HIV Infection Study (ZPHI) and the corresponding infecting partner enrolled in either the ZPHI or Swiss HIV Cohort Study. The viral genomes are pieced together, like a jigsaw puzzle, using sophisticated haplotype reconstruction algorithms such as QuasiRecomb or Haploclique. These are then compared to determine the changes/mutations, which occur in the genome as a result of transmission - being transferred to a new individual - and exposure to a new immune system. Selected ZPHI individuals are further studied to determine how their virus responds to different treatment strategies and changing immune pressure over the course of several years.

 

 

Molecular epidemiology and prevalence of drug resistance-associated mutations in drug-naive and newly diagnosed HIV-1 infected patients in Cameroon

Herbert Afegenwi Mbunkah (PhD student)

Antiretroviral therapy has turned a deadly infection with HIV-1 into a chronic life-long disease. However, this can be compromised by the development of drug resistance. In Cameroon, not all options for combination ART are available and so, it is even more important to watch out for the emergence of drug-resistant HIV-1 that leads to virological failure in treated patients. This may subsequently lead to transmission of drug-resistant HIV-1 to the uninfected, diminishing future ART options for these individuals.

We are working on determining the prevalence and recent trends in the emergence of drug resistance-associated mutations in untreated HIV patients from Cameroon, using a Next-Generation Sequencing assay suitable for all HIV-1 subtypes. Data generated will better inform optimal antiretroviral therapy delivery in Cameroon.

 

 Collaborations and support

All our projects are carried out in close collaboration with the research groups of Prof. Huldrych Günthard and Prof. Roger Kouyos here at our Division of Infectious Diseases. Together, we are a University Hospital based research team interacting with a variety of collaborators to study the pathogenesis of HIV-1 from a broad range of angles. This is possible due to our translational approach, i.e., we are studying HIV-1 pathogenesis in HIV-1 infected individuals who are longitudinally followed up in our outpatient clinic and the Swiss HIV Cohort Study over many years.

Our projects are supported by the Swiss National Science Foundation, SystemsX.ch - the Swiss Initiative in Systems Biology, the Swiss HIV Cohort Study, and a Schweizerische Bundes-Exzellenz-Stipendium to Herbert Afegenwi Mbunkah. 

Publications
Former group members

Former group members

Stefan Schmutz
Technician from 2013 - 2016, afterwards civil service

Sarah Huang, Master of Science
Master student from 2015 - 2016

Audrey Kelley, Master of Science
Master student from 2015 - 2016, afterwards PhD student in Huldrych Günthards group at the University Hospital Zurich

Kamila Caraballo Cortes. PhD
Visiting scientist in 2014 from the Medical University of Warsaw, Poland

Francesca Di Giallonardo, PhD
PhD student from 2010-2013, afterwards postdoc at the University of Sydney

Wan Lin Yang, PhD
Research assistant from 2010-2011, afterwards PhD student in Huldrych Günthard's group at University Hospital Zurich

Yannick Duport
Technician from 2011-2013, afterwards at the TU Dresden

Claudia Althaus, PhD
PhD student from 2008-2011, afterwards at the Children's Hospital Zürich