Virus evolution

Background and state of the art
Virus evolution is subject to several restrictions, which include the rather small size of the viral genome and the necessity to replicate in a host cell, i.e. to try go undetected by the immune system of the host. On the other hand, many viruses evolve very fast, as their replicases lack a proof-reading system. Thus, viruses can adapt themselves quickly to changing environmental conditions, such as treatment with antiviral drugs. Understanding virus evolution is not only of academic interest, but is necessary to predict drug-resistance mutations or the epidemic potential of certain viruses. Thus, in order to predict whether or not an outbreak of avian influenza virus constitutes a pandemic threat, it will be useful to have a complete picture of the evolutionary relationships between different influenza virus strains and their subgroups. Such an analysis has not been described for complete genomes of a large number of viral isolates. Analysis of virus evolution is complicated by the frequent occurrence of overlapping reading frames. This phenomenon is observed in retroviruses such as HIV, but also occurs in influenza virus (e.g., the overlap between the NS1 and NS2 genes). Even in large RNA virus genomes such as those of coronaviruses, overlapping reading frames do occur, disproving the current belief that this phenomenon is basically limited to small viral genomes. In fact, SARS coronavirus only became easily transmittable from human to human after a rearrangement of overlapping reading frames among the accessory genes occurred during adaption of this bat virus to the human host. The evolution of overlapping reading frames has not been analyzed in a systematic way so far.

The project
The project consists of two parts. First, an analysis of the evolution of influenza virus genes will be carried out, taking all >6,000 sequences of influenza A virus isolates into account that have been deposited in the databases. The relationships between the individual isolates will be analyzed. This will require the development of new algorithms for data sampling and presentation. Correlations of the evolutionary relationships between individual influenza virus genes with three-dimensional structures will be sought in cases where the latter are available. In the second part of the project, a systematic analysis of overlapping viral reading frames will be carried out, starting from the NS gene of influenza virus and continuing with coronaviruses and human immunodeficiency virus. The analysis will involve prediction of the secondary structure of RNA at the frameshift sites, studies of the mutations of each of the overlapping genes, and other aspects, and will be complemented by structural studies of the "overlapping proteins" (within another, experimentally oriented PhD thesis). One of the questions to be answered will be whether the evolution of both genes constitutes a compromise, or whether one of them is being optimized while the other is less-than-ideal.

People in this Project

Jiajie Zhang, B.Sc., B.Tech.Institute of Biochemistry
Thomas Martinetz, Prof. Dr. rer. nat.Investigator
Rolf Hilgenfeld, Prof. Dr. Dr. h.c.Investigator

Publications

No publications so far.