bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and characterization of novel luchacoviruses, genus
Alphacoronavirus
, in saliva and feces of meso-carnivores in the northeastern United States
Authors: Olarte-Castillo Ximena A. , Plimpton Laura , McQueary Holly , Sun Yining , Yu Y. Tina , Cover Sarah , Richardson Amy N. , Jin Yuhan , Grenier Jennifer K. , Cummings Kevin J. , Bunting Elizabeth , Diuk-Wasser Maria , Needle David , Schuler Krysten , Stanhope Michael J. , Whittaker Gary , Goodman Laura B. 
Published: October 2023

ABSTRACT

Small- to mid-sized carnivores or meso-carnivores comprise a group of diverse mammals, many of which can adapt to anthropogenically disturbed environments. Wild meso-carnivores living in urban areas may get exposed to or spread pathogens to other species, including stray/feral domestic animals. Several coronaviruses (CoVs) have been detected in domesticated and farmed meso-carnivores, but knowledge of CoVs circulating in free-ranging wild meso-carnivores remains limited. In this study, we analyzed 321 samples collected between 2016 and 2022 from 9 species of free-ranging wild meso-carnivores and stray/feral domestic cats in the northeastern United States. Using a pan-CoV PCR, we screened tissues; feces; and saliva, nasal, and rectal swabs. We detected CoV RNA in fecal and saliva samples of animals in four species: fisher (
Pekania pennanti
), bobcat (
Lynx rufus
), red fox (
Vulpes vulpes
), and domestic cat (
Felis catus
). Next-generation sequencing revealed that all these viruses belonged to the
Luchacovirus
subgenus (
Alphacoronavirus
genus), previously reported only in rodents and lagomorphs (i.e., rabbits). Genetic comparison of the 3′-end of the genome (~12,000 bp) revealed that, although the viruses detected group with and have a genetic organization similar to other luchacoviruses, they are genetically distinct from those in rodents and lagomorphs. Genetic characterization of the spike protein revealed that the meso-carnivore luchacoviruses do not have an S1/S2 cleavage motif but do have highly variable structural loops containing cleavage motifs similar to those identified in certain pathogenic CoVs. This study highlights the importance of characterizing the spike protein of CoVs in wild species for further targeted epidemiologic monitoring.

IMPORTANCE
Several coronaviruses (CoVs) have been detected in domesticated, farmed, and wild meso-carnivores, causing a wide range of diseases and infecting diverse species, highlighting their important but understudied role in the epidemiology of these viruses. Assessing the viral diversity hosted in wildlife species is essential to understand their significance in the cross-species transmission of CoVs. Our focus here was on CoV discovery in meso-carnivores in the Northeast United States as a potential “hotspot” area with high density of humans and urban wildlife. This study identifies novel alphacoronaviruses circulating in multiple free-ranging wild and domestic species in this area and explores their potential epidemiological importance based on regions of the Spike gene, which are relevant for virus-host interactions.
Zebrafish TMEM47 is an effective blocker of IFN production during RNA and DNA virus infection
Authors: Lu Long-Feng , Li Zhuo-Cong , Zhang Can , Chen Dan-Dan , Han Ke-Jia , Zhou Xiao-Yu , Wang Xue-Li , Li Xi-Yin , Zhou Li , Li Shun 
Published: October 2023

ABSTRACT

Mitochondrial antiviral signaling protein (MAVS) and stimulator of interferon (IFN) genes (STING) are crucial factors of IFN induction in RNA and DNA viral infections. However, unrestricted IFN was harmful to the host by causing cytokine storm. Here, we report that zebrafish transmembrane protein 47 (TMEM47), an IFN-negative regulator in fish, represses IFN expression stimulated by both spring viremia of carp virus (SVCV) and cyprinid herpesvirus 2, which represent RNA and DNA viruses, respectively. The mRNA level of
tmem47
was rapidly upregulated during RNA and DNA virus infection. Overexpression of TMEM47 significantly blocked SVCV- and CyHV-2-mediated IFN induction, whereas knockdown of
tmem47
promoted
ifn
transcription under these viral infections. Furthermore, TMEM47 interacted with MAVS and STING, which are considered as key factors for IFN induction during RNA and DNA viral infection. Mechanistically, both MAVS and STING were degraded by TMEM47 in an autophagy-lysosome-dependent manner, and the autophagy factor autophagy-related gene 5 (ATG5) was essential for this process. Finally, at the cellular level, MAVS- and STING-mediated antiviral capacities were significantly suppressed by TMEM47. Taken together, our results demonstrate that zebrafish TMEM47 acts as a brake to inhibit IFN production in both RNA and DNA viral infections.

IMPORTANCE
Mitochondrial antiviral signaling protein (MAVS) and stimulator of interferon (IFN) genes (STING) are key adaptor proteins required for innate immune responses to RNA and DNA virus infection. Here, we show that zebrafish transmembrane protein 47 (TMEM47) plays a critical role in regulating MAVS- and STING-triggered IFN production in a negative feedback manner. TMEM47 interacted with MAVS and STING for autophagic degradation, and ATG5 was essential for this process. These findings suggest the inhibitory function of TMEM47 on MAVS- and STING-mediated signaling responses during RNA and DNA virus infection.
A patatin-like phospholipase is important for mitochondrial function in malaria parasites
Authors: Pietsch Emma , Ramaprasad Abhinay , Bielfeld Sabrina , Wohlfarter Yvonne , Maco Bohumil , Niedermüller Korbinian , Wilcke Louisa , Kloehn Joachim , Keller Markus A. , Soldati-Favre Dominique , Blackman Michael J. , Gilberger Tim-Wolf , Burda Paul-Christian 
Published: October 2023

ABSTRACT

Plasmodium
parasites rely on a functional electron transport chain (ETC) within their mitochondrion for proliferation, and compounds targeting mitochondrial functions are validated antimalarials. Here, we localize
Plasmodium falciparum
patatin-like phospholipase 2 (
Pf
PNPLA2, PF3D7_1358000) to the mitochondrion and reveal that disruption of the
Pf
PNPLA2 gene impairs asexual replication.
Pf
PNPLA2-null parasites are hypersensitive to proguanil and inhibitors of the mitochondrial ETC, including atovaquone. In addition,
Pf
PNPLA2-deficient parasites show reduced mitochondrial respiration and reduced mitochondrial membrane potential, indicating that disruption of
Pf
PNPLA2 leads to a defect in the parasite ETC. Lipidomic analysis of the mitochondrial phospholipid cardiolipin (CL) reveals that loss of
Pf
PNPLA2 is associated with a moderate shift toward shorter-chained and more saturated CL species, implying a contribution of
Pf
PNPLA2 to CL remodeling.
Pf
PNPLA2-deficient parasites display profound defects in gametocytogenesis, underlining the importance of a functional mitochondrial ETC during both the asexual and sexual development of the parasite.

IMPORTANCE

For their proliferation within red blood cells, malaria parasites depend on a functional electron transport chain (ETC) within their mitochondrion, which is the target of several antimalarial drugs. Here, we have used gene disruption to identify a patatin-like phospholipase,
Pf
PNPLA2, as important for parasite replication and mitochondrial function in
Plasmodium falciparum
. Parasites lacking
Pf
PNPLA2 show defects in their ETC and become hypersensitive to mitochondrion-targeting drugs. Furthermore,
Pf
PNPLA2-deficient parasites show differences in the composition of their cardiolipins, a unique class of phospholipids with key roles in mitochondrial functions. Finally, we demonstrate that parasites devoid of
Pf
PNPLA2 have a defect in gametocyte maturation, underlining the importance of a functional ETC for parasite transmission to the mosquito vector.
The innate immune factor RPRD2/REAF and its role in the Lv2 restriction of HIV
Authors: Jackson-Jones Kathryn A. , McKnight Áine , Sloan Richard D. 
Published: October 2023

ABSTRACT
Intracellular innate immunity involves co-evolved antiviral restriction factors that specifically inhibit infecting viruses. Studying these restrictions has increased our understanding of viral replication, host-pathogen interactions, and pathogenesis, and represent potential targets for novel antiviral therapies. Lentiviral restriction 2 (Lv2) was identified as an unmapped early-phase restriction of HIV-2 and later shown to also restrict HIV-1 and simian immunodeficiency virus. The viral determinants of Lv2 susceptibility have been mapped to the envelope and capsid proteins in both HIV-1 and HIV-2, and also viral protein R (Vpr) in HIV-1, and appears dependent on cellular entry mechanism. A genome-wide screen identified several likely contributing host factors including members of the polymerase-associated factor 1 (PAF1) and human silencing hub (HUSH) complexes, and the newly characterized regulation of nuclear pre-mRNA domain containing 2 (RPRD2). Subsequently, RPRD2 (or RNA-associated early-stage antiviral factor) has been shown to be upregulated upon T cell activation, is highly expressed in myeloid cells, binds viral reverse transcripts, and potently restricts HIV-1 infection. RPRD2 is also bound by HIV-1 Vpr and targeted for degradation by the proteasome upon reverse transcription, suggesting RPRD2 impedes reverse transcription and Vpr targeting overcomes this block. RPRD2 is mainly localized to the nucleus and binds RNA, DNA, and DNA:RNA hybrids. More recently, RPRD2 has been shown to negatively regulate genome-wide transcription and interact with the HUSH and PAF1 complexes which repress HIV transcription and are implicated in maintenance of HIV latency. In this review, we examine Lv2 restriction and the antiviral role of RPRD2 and consider potential mechanism(s) of action.
Cyberlindnera jadinii
and
Kluyveromyces lactis
, two fungi used in food processes, have potential probiotic effects on gut inflammation
Authors: Hugot Cindy , Poirier Maxime , Spatz Madeleine , Da Costa Gregory , Michaudel Chloé , Lapiere Alexia , Danne Camille , Martin Valérie , Langella Philippe , Sokol Harry , Michel Marie-Laure , Boyaval Patrick , Richard Mathias L. 
Published: October 2023

ABSTRACT

Many strains have been used and selected by the food industry for their capacities to ferment, produce flavors, or produce heterologous molecules. Very little is known about the diversity of foodborne yeasts and their potential effect on gut microbiota and gut health. We initiated a complete characterization of five strains belonging to five species with a long history of safe use in food:
Cyberlindnera jadinii
,
Debaryomyces hansenii
,
Kazachstania unispora
,
Kluyveromyces lactis
, and
Pichia membranifaciens
, with a focus on their capacity to protect against gut inflammation using an
in vivo
dextran sodium sulfate-induced colitis model in mice.
C. jadinii
and
K. lactis
living cells showed a clear reduction in mouse sensitivity to colitis
in vivo
. Interestingly, we observed that
C. jadinii
had the capacity to survive transit in the gut, while
K. lactis
did not. We demonstrated that
C. jadinii
was unable to efficiently adhere to epithelial cells and did not survive more than 24 to 48 h in the gut. Transcriptomic analysis using NanoString technology suggested a potential role of IL-8 through Mif and Fkbp5 in the effect of
C. jadinii
on the immune system. Bacterial and fungal microbiota characterization showed a modification of both microbiota after
C. jadinii
treatment, with a significant increase in positive microorganisms and a decrease in pathobionts. Altogether, these data suggest that both
C. jadinii
and
K. lactis
strains have potential as probiotic yeast strains to fight against inflammation in the gut, but further studies are needed to understand the mechanisms by which these strains act on gut health.

IMPORTANCE
The food industry has always used many strains of microorganisms including fungi in their production processes. These strains have been widely characterized for their biotechnological value, but we still know very little about their interaction capacities with the host at a time when the intestinal microbiota is at the center of many pathologies. In this study, we characterized five yeast strains from food production which allowed us to identify two new strains with high probiotic potential and beneficial effects in a model of intestinal inflammation.
Glaesserella parasuis
QseBC two-component system senses epinephrine and regulates
capD
expression
Authors: Sun Ju , Wen Siting , Wang Zhichao , Liu Wei , Lin Yan , Gu Jiayun , Mao Weiting , Xu Xiaojuan , He Qigai , Cai Xuwang 
Published: October 2023

ABSTRACT

Glaesserella parasuis
, a common inhabitant of the upper respiratory tract of pigs, is the etiological agent of Glässer’s disease, which is characterized by fibrinous polyserositis, polyarthritis, and meningitis. Decreased production of capsular polysaccharide (CPS) promotes bacterial adhesion and uptake, whereas maximal expression of CPS is essential to evade the host immune response. For bacterial survival under highly variable host conditions, a coordinated regulation of CPS expression is necessary. In the present study, we investigated how epinephrine (Epi) affects the CPS production, biofilm formation, and adhesion ability of
G. parasuis
, as well as the specific mechanism of
G. parasuis
changes in response to Epi. The results demonstrated that Epi stimulation dramatically inhibited CPS expression, and both the action of Epi and the deletion of CPS biosynthesis gene
capD
had detrimental impacts on biofilm formation, and had the enhanced ability for cell adhesion. QseBC two-component system is a typical adrenaline-sensing system in bacteria. In the present study, by quantitative real-time PCR, Western blot, and electrophoretic mobility shift assay, we discovered that in the presence of Epi,
G. parasuis
negatively regulated
capD
expression
via
the interaction of QseB with the promoter of
capD
, thereby affecting the synthesis of CPS. In conclusion, we explored the impact of Epi on CPS synthesis and defined its regulatory mechanism in
G. parasuis
for the first time, which provides an important theoretical basis for understanding the pathogenic mechanism of
G. parasuis
.

IMPORTANCE

The key bacterial pathogen
Glaesserella parasuis
, which can cause Glässer’s disease, has caused significant financial losses to the swine industry worldwide. Capsular polysaccharide (CPS) is an important virulence factor for bacteria, providing the ability to avoid recognition and killing by the host immune system. Exploring the alteration of CPS synthesis in
G. parasuis
in response to epinephrine stimulation can lay the groundwork for revealing the pathogenic mechanism of
G. parasuis
as well as providing ideas for Glässer’s disease control.
Characteristics of respiratory viruses’ circulation through a six-year period (2016–2022) in a pediatric population in Normandy, France, and the impact of COVID-19 pandemic
Authors: Dina J. , Moisan A. , Thibon P. , Creveuil C. , Adnet J. , Vabret A. , Brouard J. , Plantier J. C. 
Published: October 2023

ABSTRACT
The impact of COVID-19 on the circulation of respiratory viruses has highlighted the need for ongoing surveillance and preparedness for emerging infectious diseases. The aim of this study was to provide information on the dynamics of respiratory viruses in pediatric populations to inform public health policies and strategies for the prevention and control of respiratory infections. This study analyzed data on the detection of respiratory viruses in pediatric populations from 2016 to 2022. The weekly number of tests and positive results for respiratory viruses were collected and analyzed from the two major university hospitals, Caen and Rouen. Different assays, including multiplex panels and rapid detection kits, were used for testing. The study analyzed the epidemiological trends of respiratory viruses in a French region during the COVID-19 pandemic. The data set included 37,969 tests, with a significant increase in the number of tests in 2020–2021 and 2021–2022. The rate of positive tests fell below 50% in 2021–2022. Enteroviruses (EV)/rhinoviruses (RV) and respiratory syncytial viruses (RSV) were the most frequently identified viruses, except in 2021–2022, when Flu ranked second. The Flu epidemic appeared slightly earlier in 2021–2022 and lasted for 25 weeks, with a doubling time of 4.03. The RSV epidemic occurred earlier in 2021–2022 and had similar dynamics to pre-pandemic years. EV/RV continued to circulate throughout the lockdowns, while low numbers of other viruses were detected. Our results emphasize the importance of continuing active surveillance of respiratory virus circulation and the need for new recommendations for respiratory virus detection in pediatric patients.

IMPORTANCE
The report highlights an epidemiological change in the circulation of respiratory viruses in pediatric populations due to strategies adopted against COVID-19 pandemic. COVID-19 has resulted in a significant increase in requests for multiplex respiratory research to identify the virus responsible for the symptoms. The diagnostic needs have increased, and the number of samples analyzed in 2021–2022 is equal to the samples analyzed over the four epidemic periods preceding the pandemic. The report suggests the importance of active surveillance of respiratory viruses' circulation and new recommendations for respiratory virus detection in pediatric patients.
Transrenal
Mycobacterium tuberculosis
DNA in pulmonary tuberculosis patients during the first 14 days of treatment
Authors: Kontsevaya Irina , Heyckendorf Jan , Koops Frauke , Hillemann Doris , Goldmann Torsten , Upton Caryn M. , De Jager Veronique , Diacon Andreas , Lange Christoph 
Published: October 2023

ABSTRACT

We assessed the performance of a novel real-time PCR-based transrenal DNA (trDNA) assay for the specific detection of
Mycobacterium tuberculosis
as a candidate marker of the early anti-tuberculosis therapy response. The study was performed on 288 urine samples from 72 tuberculosis patients collected at baseline and days 3, 7, and 14 of treatment with amoxicillin-clavulanic acid alone or in combination with meropenem, ertapenem, optimized-dose rifampicin, or standard treatment control in South Africa. trDNA was detected in one-third of the samples. The highest proportion of positive PCR results (cycle threshold < 36) was observed on days 3 and 7, reflecting the point in time when maximum bacterial killing and disintegration are expected. When analyzed by study arms, the trend was observed in groups treated with active antibiotics affecting cell wall integrity (meropenem, control) but not in inactive drugs (ertapenem, amoxicillin/clavulanic acid alone) or active drugs not affecting the cell wall (rifampicin). Overall, however, the trDNA assay did not correlate well with sputum culture-based decline of viable bacteria. This is possibly due to trDNA reflecting the killing of both culturable and non-culturable bacteria and should be explored further.

IMPORTANCE

This study presents the results of the evaluation of a novel method for the detection of
Mycobacterium tuberculosis
, the causative agent of tuberculosis, in urine. Detecting parts of the mycobacteria in urine is of particular interest as it allows us to use a sample that is easy to obtain and that does not require uncomfortable procedures or safety precautions like obtaining sputum for culture, which is the most commonly used sample in the diagnosis of tuberculosis. In certain groups of individuals who cannot produce sputum, for example, children, non-sputum-based methods have particular importance. We found that the method tested was able to detect bacterial killing by active antibiotics that disrupt the cell wall and lead to fragmentation of bacteria. However, the assay can't detect inactive bacteria or bacteria that are active with an intact cell wall.
Integrative DNA methylome and transcriptome analysis reveals DNA adenine methylation is involved in
Salmonella enterica
Typhimurium response to oxidative stress
Authors: Zhang Wenting , Lyu Lin , Xu Zhihiong , Ni Jinjing , Wang Danni , Lu Jie , Yao Yu-Feng 
Published: October 2023

ABSTRACT

Salmonella
could survive and replicate in macrophages, where it encounters multiple stresses. Deficiency of a DNA adenine methyltransferase impairs the survival of
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) in hydrogen peroxide. To investigate whether DNA methylation is involved in the expression of oxidative stress-responsive genes, we combined RNA-seq and single-molecule real-time sequencing to integrate transcriptome and methylome analysis. Here, we show that (i) the entire amount of m6A GATC remains stable during oxidative stress; (ii) no significant association is observed between DNA methylation and transcription level in most genes; (iii) coincidence of level change between transcription and m6A GATC in the regulatory regions is identified in 49 genes under oxidative stress. Some of them are known to contribute to bacterial defenses against oxidative stress through reducing H
2
O
2
levels, directing aberrant protein product degradation and inducing outer membrane protein expression. Specifically, the transcription level of
ahpCF
is negatively correlated to the m6A GATC level in its regulatory region. The transcription of
smpB
is elevated along with the decrease in m6A level at position 2,879,954 on the minus strand. In contrast, mRNA levels of
STM14_2773
and
ycfR
are positively correlated with m6A GATC content in their regulatory regions. Highly stable DNA methylome and coupled change of m6A GATC with gene expression in specific positions suggest that DNA methylation homeostasis at genome-wide and plasticity in specific regions are crucial for bacterial response to oxidative stress. These findings provide new insights into the epigenetic regulatory mechanisms of gene expression in
S
. Typhimurium in the host microenvironment.

IMPORTANCE

The intracellular pathogen
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) comes across a wide variety of stresses from entry to dissemination, such as reactive oxygen species. To adapt itself to oxidative stress,
Salmonella
must adopt various and complex strategies. In this study, we revealed that DNA adenine methyltransferase was essential for
S
. Typhimurium to survive in hydrogen peroxide. We then screened out oxidative stress-responsive genes that were potentially regulated by DNA methylation in
S
. Typhimurium. Our results show that the DNA methylome is highly stable throughout the genome, and the coupled change of m6A GATC with gene expression is identified in only a few positions, which suggests the complexity of the DNA methylation and gene expression regulation networks. The results may shed light on our understanding of m6A-mediated gene expression regulation in bacteria.
Features of the Mechanism of Proton Transport in ESR, Retinal Protein from Exiguobacterium sibiricum
Authors: Petrovskaya Lada E. , Siletsky Sergei A. , Mamedov Mahir D. , Lukashev Eugene P. , Balashov Sergei P. , Dolgikh Dmitry A. , Kirpichnikov Mikhail P. 
Published: October 2023

Abstract
Retinal-containing light-sensitive proteins – rhodopsins – are found in many microorganisms. Interest in them is largely explained by their role in light energy storage and photoregulation in microorganisms, as well as the prospects for their use in optogenetics to control neuronal activity, including treatment of various diseases. One of the representatives of microbial rhodopsins is ESR, the retinal protein of Exiguobacterium sibiricum. What distinguishes ESR from homologous proteins is the presence of a lysine residue (Lys96) as a proton donor for the Schiff base. This feature, along with the hydrogen bond of the proton acceptor Asp85 with the His57 residue, determines functional characteristics of ESR as a proton pump. This review examines the results of ESR studies conducted using various methods, including direct electrometry. Comparison of the obtained data with the results of structural studies and with other retinal proteins allows us to draw conclusions about the mechanisms of transport of hydrogen ions in ESR and similar retinal proteins.