Molecular Virology
Focusing on the causative agent of AIDS

Leading international scientists at Ulm’s Institute of Molecular Virology are conducting research into how the causative agent of AIDS adapted to humans after zoonotic transmission from greater apes. The Institute has also developed into a Centre for peptide research: scientists identify HIV inhibitors and enhancers produced by the body, with the aim, one day, of defeating the immune-deficiency disease.

Members of the Institute of Molecular Virology at Ulm University Hospital
Members of the Institute of Molecular Virology at Ulm University Hospital

AntiVirome

Research Project

AntiVirome - A combined evolutionary and proteomics approach to the discovery, induction and application of antiviral immunity

Project Leader

Prof Frank Kirchhoff

Amount of funding

1,9 Millionen €

Programme and Sponsor

ERC Advanced Grant by the European Research Counsil

Funding period

2012 - 2016

Contact

Prof Frank Kirchhoff
Institute for Molecular Virology

Origin of HIV and inhibitors produced by the body
Ulm’s Institute of Molecular Virology sets international standards

More than 35 million people around the globe live with the human immunodeficiency virus (HIV), and about the same number of individuals has already died from AIDS. Thanks to new anti-HIV drug combinations, HIV infected people in industrialised countries now have an almost normal life expectancy. However, there is still no cure for the disease. In addition, the drugs used to treat AIDS often have side effects, and are not available to all patients, particularly in Africa and other developing countries.

At Ulm’s Institute of Molecular Virology, renowned AIDS researchers contribute to combat the causative agent that destroys the human immune system. In order to gain a better understanding of the virus, they concentrate not only on its genesis, but also on searching for HIV inhibitors and enhancers produced naturally in the body, which could lead to the development of new drugs.

The causative agents of AIDS were transmitted from chimpanzees and gorillas to humans in the first half of the previous century. However, only one of the four or more independent transmissions of simian immunodeficiency viruses (SIVs) from primates to humans is responsible for the global spread of AIDS. Scientists led by Prof Frank Kirchhoff are investigating why this was the case. The Head of the Institute of Molecular Virology at Ulm and Leibniz prize-winner (Link) is considered to be one of the world’s leading AIDS researchers.

Origin of HIV-1. Simian immunodeficiency viruses infecting chimpanzees arose by recombination of viruses now found in red-capped mangabeys and Cercopithecus monkeys and were subsequently transmitted to humans.
Origin of HIV-1. Simian immunodeficiency viruses infecting chimpanzees arose by recombination of viruses now found in red-capped mangabeys and Cercopithecus monkeys and were subsequently transmitted to humans.

Researchers at Ulm managed to demonstrate that only the pandemic M (major) group of HIV-1 developed a Vpu (viral protein U) protein (Link) that potently counteracts the antiretroviral factor “tetherin” and simultaneously prevents the transport of CD4 (the primary receptor of HIV) to the cell surface. Thus, unlike other HIV-1 groups, the M group is optimally adapted to the human host.

This finding is not only important for basic research. A deeper understanding of the evolution of the causative agent of AIDS and of human defence mechanisms could pave the way for innovative therapeutic approaches. For example, the researchers are searching for further antiviral factors that affect the spread and pathogenicity of HIV-1.

HIV particles trapped at the surface of cells expressing the antiviral factor tetherin.
HIV particles trapped at the surface of cells expressing the antiviral factor tetherin.

The human body - a "pharmacy"

In the search for new active substances, Ulm’s researchers are also looking for agents in body fluids that inhibit the HI virus. In this way, they came across a peptide in human blood called “VIRIP” that inhibits the anchorage of the causative agent to the host cell, preventing infection. Targeted modifications to the peptide can increase its effectiveness even further.

Research into such substances produced by the body is carried out at the “Ulm Centre for Peptide Pharmaceuticals” (UPEP), established in 2013. This interdisciplinary establishment, which acts as a link between science and the pharmaceutical industry, seeks to develop drugs based on antimicrobial or anticancer peptides produced by the body to fight a number of diseases.

During their investigations, Ulm’s AIDS researchers also discovered fibrils in human semen that promote infection with HIV. These “sticky rods” bind pathogen particles, making it easier for them to adhere to the target cell. Without these fibrils, called SEVI (semen-derived enhancers of infection), a lot more viral particles are required to infect a cell. Inhibiting the interaction of fibrils with viral particles provides a new starting point for preventing the sexual transmission of HIV. In addition, analogous fibrils may allow scientists to enhance retroviral gene transfer in basic research and therapeutic applications.

The outstanding scientific achievements of the Institute of Molecular Virology is demonstrated, amongst others, by the awarding of an Advanced Grant (Link) worth € 2 million by the European Research Council. Backed by this funding instrument, acquired by Prof Kirchhoff in 2012, the scientists wish to explore how the HI virus bypasses the human immune system, and how to strengthen natural defence mechanisms. They are also involved in additional projects, in which they collaborate closely with other scientific institutions, in particular the Institute of Organic Chemistry III, and the Institute of Virology at Ulm University Medical Centre. Measures have also been taken to ensure young researchers are recruited: host-pathogen interaction is a key area addressed at the “excellent” International Graduate School in Molecular Medicine at Ulm University.

Amyloid fibril with associated HIV particles.
Amyloid fibril with associated HIV particles.