Virus capsid reaches the cell nucleus intact

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10.02.2021 17:15

New piece of the HIV infection puzzle researched: virus capsid enters the cell nucleus intact

Cooperation project between Heidelberg University Hospital and the European Molecular Biology Laboratory: Combination of high-resolution imaging methods provides detailed insight into infection processes inside cells / publication in Cell

Scientists from the Center for Infectious Diseases at Heidelberg University Hospital and the European Molecular Biology Laboratory in Heidelberg (EMBL) have for the first time succeeded in mapping the HIV virus as it is transported into the nucleus of the infected cell. The electron tomographic images show: The protein shell of the virus passes through the nuclear pore as a whole and only breaks inside the cell nucleus, where it releases the genetic information of the virus. The work recently published in the specialist journal Cell clarifies an important mechanism in the integration of the virus genome in the infected cells.

The human immunodeficiency virus (HIV-1) primarily infects certain cells of the immune system and in this way massively weakens the body’s defense against disease. The genetic material of the virus is securely packaged in a cone-shaped protein capsule, the capsid made up of individual hexagonal parts. It is well known how the capsid gets through the cell envelope into the interior of the cell during infection. So far, however, it has not been clear how the viral genetic material gets from the capsid into the cell nucleus, where it triggers the formation of new viruses.

This is where the work of the Heidelberg cooperation comes into play. With the help of newly developed methods for the three-dimensional representation of molecular complexes in virus-infected cells, the scientists succeeded in imaging the virus capsid as it was transported into the nucleus. “Until now, it was assumed that the capsid would not fit through the pores,” explains Prof. Dr. Hans-Georg Kräusslich, Medical Director of the Center for Infectious Diseases at Heidelberg University Hospital. “The question of how the virus genome gets into the cell nucleus, however, is essential for its reproduction. Our results therefore support the search for new target structures for future therapeutic approaches. ”Although the current treatment options can suppress the multiplication of viruses in the body, a real cure with elimination of the viruses is not yet possible.

High resolution imaging platforms

For a detailed look at the inner workings of infected immune cells in the laboratory, the scientists used high-resolution imaging techniques: With the help of the Electron Microscopy Core Facility (EMCF) of Heidelberg University and the cryo-electron microscopy service platform (cryo-EM-EMBL) of EMBL, they combined various Methods of light and electron microscopy and reconstructed three-dimensional images of the molecular structures from the data. Thus, the composition and architecture of the viral complexes and their interaction with the cellular structures could be displayed in high resolution. “The close cooperation between our two facilities and the combination of specialized technology has contributed to adding another piece of the HIV infection puzzle to the overall picture,” says Dr. Martin Beck, former research group leader at EMBL and since 2019 Director and Scientific Member at the Max Planck Institute for Biophysics in Frankfurt.

The cooperation project emerged from the good cooperation between the research groups of the Collaborative Research Center “Integrative Analysis of the Replication and Spread of Pathogenic Pathogens”. The aim of the SFB, headed by Prof. Kräusslich, is to elucidate the molecular processes of the multiplication and spread of pathogens in order to understand the basic mechanisms of infection.

Scientific contact:

Prof. Dr. with. Hans-Georg Kräusslich
Center for Infectiology, Virology
Heidelberg University Hospital
Email: [email protected]
Tel.: 06221 56-5001

Dr. Martin Beck
Max Planck Institute for Biophysics
Frankfurt am Main
Email: [email protected]
Tel: 069 6303-3500

Originalpublikation:

Cone-shaped HIV-1 capsids are transported through intact nuclearpores, Vojtech Zila et. al., Cell 2021
doi 10.1016/j.cell.2021.01.025

Further information:

https://www.klinikum.uni-heidelberg.de/zentrum-fuer-infektiologie/virologie
https://www.biophys.mpg.de/molekulare-soziologie

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