Archaeal host cell recognition and viral binding of HFTV1 to its Haloferax host

Viruses are highly abundant and the main predator of microorganisms. Microorganisms of each domain of life are infected by dedicated viruses. Viruses infecting archaea are genomically and structurally highly diverse. Archaea are undersampled for viruses in comparison with bacteria and eukaryotes. Consequently, the infection mechanisms of archaeal viruses are largely unknown, and most available knowledge stems from viruses infecting a select group of archaea, such as crenarchaea. We employed Haloferax tailed virus 1 (HFTV1) and its host, Haloferax gibbonsii LR2-5, to study viral infection in euryarchaea. We found that HFTV1, which has a siphovirus morphology, is virulent, and interestingly, viral particles adsorb to their host several orders of magnitude faster than most studied haloarchaeal viruses. As the binding site for infection, HFTV1 uses the cell wall component surface (S)-layer protein. Electron microscopy of infected cells revealed that viral particles often made direct contact with their heads to the cell surface, whereby the virion tails were perpendicular to the surface. This seemingly unfavorable orientation for genome delivery might represent a first reversible contact between virus and cell and could enhance viral adsorption rates. In a next irreversible step, the virion tail is orientated toward the cell surface for genome delivery. With these findings, we uncover parallels between entry mechanisms of archaeal viruses and those of bacterial jumbo phages and bacterial gene transfer agents.IMPORTANCE Archaeal viruses are the most enigmatic members of the virosphere. These viruses infect ubiquitous archaea and display an unusually high structural and genetic diversity. Unraveling their mechanisms of infection will shed light on the question if entry and egress mechanisms are highly conserved between viruses infecting a single domain of life or if these mechanisms are dependent on the morphology of the virus and the growth conditions of the host. We studied the entry mechanism of the tailed archaeal virus HFTV1. This showed that despite "typical" siphovirus morphology, the infection mechanism is different from standard laboratory models of tailed phages. We observed that particles bound first with their head to the host cell envelope, and, as such, we discovered parallels between archaeal viruses and nonmodel bacteriophages. This work contributes to a better understanding of entry mechanisms of archaeal viruses and a more complete view of microbial viruses in general.Archaeal viruses are the most enigmatic members of the virosphere. These viruses infect ubiquitous archaea and display an unusually high structural and genetic diversity.Peer reviewe

Growth Phase Dependent Cell Shape of Haloarcula

Several haloarchaea are reported to be pleomorphic, while others exhibit remarkable shapes, such as squares. Recently, Haloferax volcanii was found to alter its morphology during growth. Cells are motile rods in early exponential phase, and immotile plates in stationary phase. It is unknown if this growth phase dependent cell shape alteration is a specific feature of Hfx. volcanii, or conserved amongst haloarchaea. Here, we studied the cell shape and motility of two haloarchaea species Haloarcula hispanica and Haloarcula californiae. With a combination of light and electron microscopy, we observed that both strains undergo a growth phase dependent morphological development, albeit in a slightly different fashion as Hfx. volcanii. For both Haloarcula strains, the cell size is changing throughout growth. Cell shape seems to be related with motility, as highly motile cells on semi-solid agar plates are predominantly rod-shaped. We conclude that the growth phase dependent cell morphology alteration might be a common feature amongst haloarchaea, and that cell shape is generally linked with a motile life style. The conservation of this phenomenon underscores the importance of studies of the molecular mechanisms regulating cell shape in archaea

Growth Phase Dependent Cell Shape of Haloarcula

Several haloarchaea are reported to be pleomorphic, while others exhibit remarkable shapes, such as squares. Recently, Haloferax volcanii was found to alter its morphology during growth. Cells are motile rods in early exponential phase, and immotile plates in stationary phase. It is unknown if this growth phase dependent cell shape alteration is a specific feature of Hfx. volcanii, or conserved amongst haloarchaea. Here, we studied the cell shape and motility of two haloarchaea species Haloarcula hispanica and Haloarcula californiae. With a combination of light and electron microscopy, we observed that both strains undergo a growth phase dependent morphological development, albeit in a slightly different fashion as Hfx. volcanii. For both Haloarcula strains, the cell size is changing throughout growth. Cell shape seems to be related with motility, as highly motile cells on semi-solid agar plates are predominantly rod-shaped. We conclude that the growth phase dependent cell morphology alteration might be a common feature amongst haloarchaea, and that cell shape is generally linked with a motile life style. The conservation of this phenomenon underscores the importance of studies of the molecular mechanisms regulating cell shape in archaea

The viral susceptibility of the <i>Haloferax</i> species

Viruses can infect members of all three domains of life. However, little is known about viruses infecting archaea and the mechanisms that determine their host interactions are poorly understood. Investigations of molecular mechanisms of viral infection rely on genetically accessible virus–host model systems. Euryarchaea belonging to the genus Haloferax are interesting models, as a reliable genetic system and versatile microscopy methods are available. However, only one virus infecting the Haloferax species is currently available. In this study, we tested ~100 haloarchaeal virus isolates for their infectivity on 14 Haloferax strains. From this, we identified 10 virus isolates in total capable of infecting Haloferax strains, which represented myovirus or siphovirus morphotypes. Surprisingly, the only susceptible strain of all 14 tested was Haloferax gibbonsii LR2-5, which serves as an auspicious host for all of these 10 viruses. By applying comparative genomics, we shed light on factors determining the host range of haloarchaeal viruses on Haloferax. We anticipate our study to be a starting point in the study of haloarchaeal virus–host interaction

The Viral Susceptibility of the Haloferax Species

Viruses can infect members of all three domains of life. However, little is known about viruses infecting archaea and the mechanisms that determine their host interactions are poorly understood. Investigations of molecular mechanisms of viral infection rely on genetically accessible virus–host model systems. Euryarchaea belonging to the genus Haloferax are interesting models, as a reliable genetic system and versatile microscopy methods are available. However, only one virus infecting the Haloferax species is currently available. In this study, we tested ~100 haloarchaeal virus isolates for their infectivity on 14 Haloferax strains. From this, we identified 10 virus isolates in total capable of infecting Haloferax strains, which represented myovirus or siphovirus morphotypes. Surprisingly, the only susceptible strain of all 14 tested was Haloferax gibbonsii LR2-5, which serves as an auspicious host for all of these 10 viruses. By applying comparative genomics, we shed light on factors determining the host range of haloarchaeal viruses on Haloferax. We anticipate our study to be a starting point in the study of haloarchaeal virus–host interactions

The Viral Susceptibility of the Haloferax Species

Viruses can infect members of all three domains of life. However, little is known about viruses infecting archaea and the mechanisms that determine their host interactions are poorly understood. Investigations of molecular mechanisms of viral infection rely on genetically accessible virus–host model systems. Euryarchaea belonging to the genus Haloferax are interesting models, as a reliable genetic system and versatile microscopy methods are available. However, only one virus infecting the Haloferax species is currently available. In this study, we tested ~100 haloarchaeal virus isolates for their infectivity on 14 Haloferax strains. From this, we identified 10 virus isolates in total capable of infecting Haloferax strains, which represented myovirus or siphovirus morphotypes. Surprisingly, the only susceptible strain of all 14 tested was Haloferax gibbonsii LR2-5, which serves as an auspicious host for all of these 10 viruses. By applying comparative genomics, we shed light on factors determining the host range of haloarchaeal viruses on Haloferax. We anticipate our study to be a starting point in the study of haloarchaeal virus–host interactions

A single dose of the Biontech/Pfizer BNT162b2 vaccine protected elderly residents from severe COVID‐19 during a SARS‐coronavirus‐2 outbreak in a senior citizen home in Germany

Background: A total of 62/66 (93.9%) residents in a senior citizen home in Bremen, Germany, received the first dose of the Biontech/Pfizer vaccine BNT162b2 on December 27th 2020. After routine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen tests showed positive results on January 5th, all residents and staff were tested by RT-PCR. Results: Nine staff members and 23 residents had a positive result. PCR positive staff members reported mild to severe COVID-19 symptoms, one was hospitalized. None of them had been vaccinated. In contrast, the vaccinated residents reported no or only mild symptoms. Sequencing of the SARS-CoV-2 genomes of infected individuals revealed a monophyletic origin of the outbreak within the PANGO lineage B.1.177.86. Conclusions: In summary, our data show that partial vaccination prevented severe COVID-19 among the residents during this local SARS-CoV-2 outbreak, suggesting a high effectiveness of even a single vaccine dose, but also emphasize that asymptomatic individuals might still be carriers/spreaders

New Features on the Expression and Trafficking of mGluR1 Splice Variants Exposed by Two Novel Mutant Mouse Lines

Metabotropic glutamate receptors (mGluRs) couple to G-proteins to modulate slow synaptic transmission via intracellular second messengers. The first cloned mGluR, mGluR1, regulates motor coordination, synaptic plasticity and synapse elimination. mGluR1 undergoes alternative splicing giving rise to four translated variants that differ in their intracellular C-terminal domains. Our current knowledge about mGluR1 relates almost entirely to the long mGluR1α isoform, whereas little is known about the other shorter variants. To study the expression of mGluR1γ, we have generated by means of the CRISPR/Cas9 system a new knock-in (KI) mouse line in which the C-terminus of this variant carries two short tags. Using this mouse line, we could establish that mGluR1γ is either untranslated or in amounts that are undetectable in the mouse cerebellum, indicating that only mGluR1α and mGluR1β are present and active at cerebellar synapses. The trafficking and function of mGluR1 appear strongly influenced by adaptor proteins such as long Homers that bind to the C-terminus of mGluR1α. We generated a second transgenic (Tg) mouse line in which mGluR1α carries a point mutation in its Homer binding domain and studied whether disruption of this interaction influenced mGluR1 subcellular localization at cerebellar parallel fiber (PF)-Purkinje cell (PC) synapses by means of the freeze-fracture replica immunolabeling technique. These Tg animals did not show any overt behavioral phenotype, and despite the typical mGluR1 perisynaptic distribution was not significantly changed, we observed a higher probability of intrasynaptic diffusion suggesting that long Homers regulate the lateral mobility of mGluR1. We extended our ultrastructural analysis to other mouse lines in which only one mGluR1 variant was reintroduced in PC of mGluR1-knock out (KO) mice. This work revealed that mGluR1α preferentially accumulates closer to the edge of the postsynaptic density (PSD), whereas mGluR1β has a less pronounced perijunctional distribution and, in the absence of mGluR1α, its trafficking to the plasma membrane is impaired with an accumulation in intracellular organelles. In conclusion, our study sets several firm points on largely disputed matters, namely expression of mGluR1γ and role of the C-terminal domain of mGluR1 splice variants on their perisynaptic clustering

Factors associated with self-rated health status in university students: a cross-sectional study in three European countries

Mikolajczyk RT, Brzoska P, Maier C, et al. Factors associated with self-rated health status in university students: a cross-sectional study in three European countries. BMC Public Health. 2008;8(1): 215.Background: Self-rated health status (SRHS) is a reliable and valid measure for assessing the subjective and objective health of individuals. Previous studies have either focused predominantly on the elderly or investigated only a narrow range of factors potentially associated with SRHS. In examining student populations, these past studies were limited to single countries. The objectives of this study were to assess which candidate variables were independently associated with SRHS in university students, to compare these variables by country and by gender, and to investigate which of the variables was most important as a rating frame for SRHS. Methods: The data is from the Cross-National Student Health Survey, conducted in 2005 in universities in Germany, Bulgaria, and Poland (n = 2103; mean age = 20.7 years). SRHS was assessed with a single question using a five-point scale ranging from "excellent" to "poor". The study also measured a wide range of variables including: physical and psychological health, studying, social contacts/social support, and socio-demographic status. Results: Psychosomatic complaints (considered an aspect of physical health and, adjusted for psychological health) were the most important indicators in forming a rating frame for students' SRHS. There were few differences in the effects of variables associated with SRHS by gender (well-being: a measure of psychological health) and the variables associated with SRHS by country (well-being and self-efficacy). The remaining variables showed homogenous effects for both genders and for all three countries. Conclusion: The results suggest that SRHS can be reasonably used to compare students' health across countries. SRHS is affected by different physical, psychological and psychosomatic aspects of health; however, its strongest association is with psychosomatic complaints

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery