#FEMSmicroBlog: The incredible world of archaeal viruses


Like all organisms from the three domains of life, archaea suffer from viral infections. While molecular mechanisms for viruses infecting humans or bacteria are well characterized, archaeal viruses are still understudied due to the difficulty of cultivating archaeal strains or sampling bias. The short review “Archaeal virus entry and egress” gives an overview of the current state of knowledge on the infection strategies of archaeal viruses, as summarised by Bastian Kuiper, Anna Schöntag and Tessa Quax in this #FEMSmicroBlog. #FascinatingMicrobes


The uniqueness of archaea and their viruses

Archaeal viruses have a broad range of morphologies, with many families showing unique shapes. In comparison to other viruses, most aspects of the infection cycles of archaeal viruses and their genomic features remain unexplored.

However, recent advancements in genetic tools and imaging techniques have helped to identify new archaeal viral receptors. These discoveries shed some light on the viral release mechanisms helping us better understand the archaeal world.

For a successful infection, the archaeal cell envelope is the first barrier for archaeal viruses to overcome. In contrast to bacteria and eukaryotes, the archaeal cell membrane consists of isoprenoid-based ether-linked membrane lipids.

Additionally, the archaeal cell envelope is made of highly glycosylated surface-layer proteins with various surface filaments. These filaments include the archaellum, comparable to the bacterial flagellum and used for motility. Additionally, archaea possess diverse pili and other cell surface filaments involved in DNA transfer and attachment.

Schematic depiction of virus interactions with the archaeal cell envelope at virus entry.
Schematic depiction of virus interactions with the archaeal cell envelope at virus entry. From Kuiper et al. (2024).


How archaeal viruses overcome the archaeal cell envelope

As some viruses interact with the surface filaments of their hosts, research focused on the interactions between archaeal viruses and their host cells. Although not yet observed, archaeal viruses are thought to attach to the extended filaments. From the tip of the filament, the virus might ‘’surf’’ to the cell surface and inject its genome into the archaea cell to reproduce.

Other viruses, mainly those infecting halophiles or methanogens, interact directly with the S-layer. One example is the extraordinary upside-down attachment of archaeal head-tailed viruses, which have similar structures to bacterial head-tailed viruses.

After reorienting itself, the virus adsorbs via its tail fibers, followed by similar infection and genome injection strategies as its bacterial counterparts. Yet, information on the mechanism of genome ejection remains scarce. Only the initial proteins potentially involved in this process have been discovered.


Zipping, lysing, and budding – a plethora of archaeal viral release strategies

The final step of the viral infection circle involves releasing the newly synthesized virions from the host cell. This results either in the complete lysis of the cell or a local disruption of the cell membrane without harming the host.

Schematic depiction of egress mechanisms of Archaeal viruses.
Schematic depiction of egress mechanisms of Archaeal viruses. From Kuiper et al. (2024).


One mechanism to exit archaeal hosts includes so-called virus-associated pyramids, mainly employed by viruses infecting hyperthermophilic hosts of Thermoproteota. Virus-associated pyramids are large, symmetric, and hollow pyramidal-structures embedded in the host cell membrane. Upon viral release, these pyramids ‘zip’ open and allow for the viruses to leave the host cell.

In contrast, archaeal head-tailed viruses are often lytic; causing complete host cell lysis. Lytic bacteriophages commonly use the holin-endolysin system, with holins forming holes in the membrane allowing for endolysins to enter and cleave the bacterial cell wall. Since the archaeal cell envelope is quite different, one can only speculate how archaeal head-tailed viruses lyse their host. One hypothesis includes degrading enzymes that were found in (pro)viruses in methanogenic archaea and cause autolysis.

Lastly, some viruses exit their hosts via budding, with parts of the host cell membrane enclosing virions into a bud and separating from the host cell. Notably, some spindle-shaped archaea viruses involve the endosomal system in a fashion similar to enveloped eukaryotic viruses.

In recent years, many studies shed light on several aspects of archaeal viruses and their infection strategies. By fully comprehending the significance of archaeal viruses on their hosts, we will gain a deeper understanding of the environmental and ecological processes influenced by archaea.


About the authors of this blog

Anna Schöntag studied Biotechnology at the Technical University of Berlin, where she obtained her BSc degree in 2018 and her MSc degree in Medical Biotechnology in 2022. During that time, she worked on protein interaction studies with cell-free synthesized S. aureus enterotoxins in the group of Dr. Anne Zemella and Dr. Marlitt Stech at the Fraunhofer IZI-BB in Potsdam. Anna is currently a PhD student in the lab of Tessa Quax at the Department of Molecular Microbiology at the University of Groningen. She studies in archaeal virus-host interactions and is interested in their entry and genome ejection strategies and investigates superinfection exclusion in archaea.

Bastiaan Kuiper studied Biomolecular Sciences at the University of Groningen, where he obtained his BSc degree in 2018. He obtained his MSC degree in 2021 for his work on ER-resident chaperone proteins in the group of Prof Dr. Ikuo Wada at Fukushima Medical University. Bastiaan is a PhD student in the lab of Tessa Quax at the Department of Molecular Microbiology at the University of Groningen. His research focuses on elucidating the egress mechanisms of haloarchaeal head-tailed viruses.

Tessa Quax is an associate professor at the University of Groningen. She focuses with her group on molecular mechanisms of infection of archaeal viruses. She obtained her PhD degree from Wageningen University and Institut Pasteur. She did post-doctoral projects at the University of Leuven, Belgium, and at the University of Freiburg in Germany. In 2019 she started her lab with the help of an Emmy Noether grant. Her work received several awards, such as an ERC starting and a Vidi grant, the KNAW (Royal Netherlands Society for Arts and Sciences) Early Career Award and Beijerinck Premium.

About this blog section

The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.

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