Unrav­el­ing univer­sal mecha­nisms of viral replication

This project, led by Prof. Dr. Dr. h.c. Ralf Barten­schlager (Heidel­berg Univer­sity) and Prof. Dr. Tessa Quax (Univer­sity of Gronin­gen), will inves­ti­gate whether archaeal viruses form special­ized repli­ca­tion compart­ments similar to those found in bacte­r­ial and eukary­otic viruses. These compart­ments help to optimize repli­ca­tion and protect viruses from host defenses. By integrat­ing struc­tural biology, cell biology, chemistry, and medicine, the project aims to uncover univer­sal viral repli­ca­tion mecha­nisms. Advanced imaging, genetic label­ing, and lipidomics will be used to study viral repli­ca­tion in archaea and compare it to other organ­isms. The results could provide new insights into viral evolu­tion, reveal novel targets for antivi­ral therapy, and help identify common princi­ples of viral repli­ca­tion across domains. In addition, the project will train young scien­tists in inter­dis­ci­pli­nary virol­ogy, foster­ing future advances in viral research. The results could have a signif­i­cant impact on both basic virol­ogy and the devel­op­ment of new antivi­ral strategies.

Viruses play a criti­cal role in ecosys­tems, shaping micro­bial commu­ni­ties and impact­ing biodi­ver­sity, human health and climate. While viruses infect organ­isms in all domains of life — archaea, bacte­ria, and eukary­otes — studies have predom­i­nantly focused on eukary­otic viruses. However, recent evidence suggests that bacte­r­ial viruses, like their eukary­otic counter­parts, form special­ized repli­ca­tion compart­ments that concen­trate essen­tial repli­ca­tion factors and provide protec­tion against host defenses. Whether archaeal viruses also use such mecha­nisms remains an open question.

This inter­dis­ci­pli­nary project, led by experts in archaeal virol­ogy and viral repli­ca­tion, aims to deter­mine whether archaeal viruses also gener­ate compart­men­tal­ized repli­ca­tion and assem­bly sites. The study will use advanced imaging techniques, includ­ing fluores­cence and cryo-electron microscopy, to visual­ize viral repli­ca­tion in archaeal cells. In addition, the project will use genetic tagging and lipidomics to analyze the molec­u­lar compo­si­tion of these poten­tial compart­ments to gain a compre­hen­sive under­stand­ing of their struc­ture and function.

By study­ing archaeal viral repli­ca­tion at multi­ple levels — struc­tural, biochem­i­cal, and evolu­tion­ary — this research aims to identify univer­sally conserved repli­ca­tion strate­gies across domains of life. Such insights will provide new perspec­tives on the origin of viruses and their evolu­tion­ary adapta­tion to differ­ent hosts. In addition, under­stand­ing the role of viral compart­ments may reveal novel targets for broad-spectrum antivi­ral strate­gies, partic­u­larly against viruses that use similar repli­ca­tion strate­gies in humans.

Beyond its scien­tific impact, this project will also contribute to the train­ing young scien­tists in cross-compart­men­tal virol­ogy. The ability to compare viral processes across archaea, bacte­ria, and eukary­otes will provide young scien­tists with a unique and integra­tive perspec­tive essen­tial for address­ing funda­men­tal questions in virol­ogy. By bridg­ing gaps between tradi­tion­ally separate fields of research, this project will help unify our under­stand­ing of viral repli­ca­tion, with impli­ca­tions for both basic science and medical applications.