|
|
Mechanisms of Viral Entry and Replication |
 |
Viruses have to use host cells to replicate their
genetic material, express viral proteins and form new virus particles. Replication cycle of enveloped viruses: A
Binding to host cell receptors |
| In that process, membrane coated (enveloped) viruses have to fuse with respective target membranes in order to deliver their genome into the host cell. Depending on the virus strain this can occur either directly with the plasma membrane (e.g. HIV) or with the endosomal membrane (e.g. Influenza). | |
| Fusion is mediated by fusion proteins of the viral
membrane. Depending on the entry pathway, fusion is triggert either by
binding of the fusion proteins to specific receptors or by the low pH in
endosomes. |
|
| Project: | Host adaptation and pathogenicity of the
influenza virus hemagglutinin. Caroline
Mair Infection of Influenza virus is mediated by its viral spike protein hemagglutinin (HA) which binds to sialic acid cell receptors of the host cell. Mutations in the HA ectodomain can cause changes in host cell specificity and viral pathogenicity. We are investigating the influence of mutations influencing the stability of HA on virus infectivity and pathogenicity. ...more |
| Afterwards the viral genetic material is transported to
the nucleus where replication and translation occurs. The first step of
the synthesis of viral proteins is the translation of the RNA or DNA
into mRNA. |
|
| Project: | Imaging of viral mRNA using sequence specific fluorescent Peptide
Nucleic Acids. Susann Kummer An early consequence of virus infection is the formation of viral mRNA. To follow both its formation and intracellular location we utilize PNA (Peptide Nucleic Acid) molecules, tagged with a fluorescent moiety. ...more |
| The expression of viral proteins occurs in the cytosol,
amplification and assembly of genetic material in the nucleus. Budding
of new viruses takes place either at the plasma membrane or at
intracellular membranes. Therefore, the viral components have to be
transported to the budding site where they are assembled in a well
controlled manner. This is a coplex process, which is not well
understood so far. |
|
| Project: | Role of matrix protein M1 in Influenza A assembly and budding.
Nadine Jungnick The major structural protein in influenza A is the matrix protein M1, if forms a shell underneath the viral membrane and encloses the ribonuclein complexes. The interaction of M1 with model membranes and viral components is investigated using recombinantly expressed M1. ...more |
| Project: | The role of Influenza ribonuclein (RNP) complexes in virus
assembly. Chris Tina Höfer In the process of virus assembly, not only the viral proteins have to be segregated selectively into the budding site, also the genetic material has to be packet into the virus core. The interaction of RNP complexes as well as nucleoprotein with other viral components is investigated using biochemical and microscopical methods. ...more |
| Project: | Lipid-raft association of the HIV glycoprotein gp41. Roland
Schwarzer It has been suggested that lipid microdomains of the host cell plasmamembrane - the so called "rafts" - play an important role for the budding of new viruses, they could be utilized as platform for the assembly of the viral components. We apply Fluorescence Lifetime Imaging Microscopy (FLIM) to detect HIV gp41 localization and co-clustering of viral proteins. ...more |
| Project: | Intracellular dynamics of HIV-GAG. Andrea Gramatica
Assembly of the human immunodeficiency virus 1 (HIV-1) is determined by a single gene that encodes a structural polyprotein precursor, Pr55 Gag polyprotein. The Gag protein is the only viral component required for the assembly of virus-like particles (VLPs). We investigate the intracellular localization of Gag, possible interactions between Gag and host cell components and the role of calcium in the Gag localization process and VLPs release. ...more |
| Recent Project: | Lateral sorting of Influenza virus Hemagglutinin in membranes.
Silvia Scolari The fusion protein of Influenza (HA) is supposed to entrap in liquid-ordered lipid domains (rafts) of the host cell before budding. In order to investigate the lipid domain location, Foerster’s energy transfer (FRET) between yfp-labelled HA transmembrane domains and a cfp raft marker is studied by fluorescence lifetime imaging microscopy (FLIM). ...more |
| Knowledge of the basic mechanisms of virus entry, fusion
and budding can provide targets for the developement of antiviral drugs. |
|
| Project: | Inhibition of Influenza Virus Activity by Sialic Acid Conjugated
Multivalent Particles. Christian Sieben Influenza virus binds to sialic acid residues of glycoproteins on the plasma membrane of the host cell. Multivalent analogues of the receptor are tested for the ability to inhibit viral infection with high potency. ...more |
While for many viruses the pathway of entering the cell is well known, for other viruses it is not. Some virus strains might even use both pathways. Knowledge of the entry pathway is essential for the understanding of the detailed fusion mechanism(s).
| Recent Project: | Entry and fusion mechanism of Mouse Hepatitis
Virus (MHV). Patricia
Eifart MHV is used as a model system to investigate the virus entry and the fusion mechanism of the S-protein of coronaviruses (SARS). ...more |
| Recent Project: | Entry Pathway of Equine arteritis virus (EAV).
Mathias Nitschke
EAV is an enveloped virus, which can cause severe problems in horse breeding. In order to find out, whether the virus utilizes the endosomal or the non-endosomal pathway, we have investigated infection of Baby Hamster Kindey cells (BHK) by EAV. ...more |