bluuebunny/crossref_metadata_2025_split huggingface dataset:
Swine RNF5 positively regulates the antiviral activity of IFITM1 by mediating the degradation of ABHD16A
Authors: Shi Xuemeng , Shen Lingyi , Chen Shuaiwu , Liu Mingyang , Wang Jingyi , Wen Xin , Liu Wei , Mao Lin , Ding Yunyun , Yu Li , Xu Jun 
Published: November 2024

ABSTRACT

Interferon-inducible transmembrane (IFITM) proteins are broad-spectrum antiviral factors that confer cellular resistance to virus invasion. α/β-Hydrolase domain-containing 16A (ABHD16A) has recently been identified as a novel depalmitoylase that can inhibit the antiviral activity of IFITM proteins by catalyzing the depalmitoyl reaction; this pattern may be crucial for the host to avoid damage caused by excessive immune response. However, it remains largely elusive about how host cells regulate the activity of ABHD16A. In the present study, we performed the AlphaFold2-based protein-protein interaction prediction and identified swine E3 ubiquitin ligase ring finger protein 5 (sRNF5) as a sABHD16A-interacting protein and negatively regulated the stability of sABHD16A. Using immunofluorescence and co-immunoprecipitation techniques, we uncovered that sRNF5 targeted sABHD16A for ubiquitination and degradation via the proteasomal pathway at residues K3 and K452. Furthermore, sABHD16A catalyzed the depalmitoylation of sIFITM1, which obstructed the antiviral function of sIFITM1, while sRNF5 caused ubiquitination of sABHD16A, which attenuated the depalmitoylation effect on sIFITM1, and consequently restored the antiviral activity of sIFITM1. Collectively, our findings demonstrate for the first time that sRNF5 positively regulates the antiviral function of sIFITM1 by mediating the degradation of sABHD16A, which expands the biological functions of RNF5 and ABHD16A in immune regulation. Moreover, our work highlights the well-designed interplay between RNF5, ABHD16A, and IFITM, which balances antiviral immune responses to avoid the disorders induced by excessive immune response.

IMPORTANCE
Interferon and interferon-stimulated genes play significant and protective roles in the host’s defense against viral infection. IFITM family proteins, which can be strongly induced by interferon, have been identified as the first line of defense to prevent invasion of various viruses. Further analysis reveals the antiviral activity of IFITMs depends on palmitoylation/depalmitoylation. Recently, we reported that ABHD16A, as the first depalmitoylase of IFITMs, negatively regulated the antiviral activity of IFITMs. However, these raise crucial questions: how ABHD16A is regulated and remained in a balanced manner? Here, we show that swine RNF5 attenuates the negative regulation of sIFITM1 against virus invasion by modifying sABHD16A through ubiquitination and guiding sABHD16A for degradation. Thus, sRNF5-sABHD16A interplay plays an indispensable role in regulating immune response and avoiding the disorders induced by elevated interferon levels. Overall, our findings extend the upstream subtle regulatory molecular mechanism of IFITMs and provide potential targets for viral disease therapy.
Canine parvovirus NS1 induces host translation shutoff by reducing mTOR phosphorylation
Authors: Wang Xinrui , Hao Xiangqi , Zhao Yaning , Xiao Xiangyu , Li Shoujun , Zhou Pei 
Published: November 2024

ABSTRACT

Canine parvovirus type 2 (CPV-2) is a member of the Parvoviridae family, characterized by its small, non-enveloped virions containing a linear single-stranded DNA genome of approximately 5 kb. Parvoviruses entirely reliant on the host cell’s division machinery for replication. In this study, we demonstrate that CPV-2 infection triggers the host translation shutoff, a process in which the nonstructural protein 1 (NS1) plays a pivotal role. Our findings indicate that the CPV-2 NS1-induced host translation shutoff is not associated with transcription, protein degradation pathways, or eIFα phosphorylation, but rather involves the reduction of phosphorylation of the mammalian target of rapamycin (mTOR). In conclusion, this research reveals that CPV-2 NS1 induces a host translation shutoff by reducing mTOR phosphorylation, a mechanism that could potentially inform the development of more efficacious control and therapeutic strategies for CPV-2 and other parvoviral infections.

IMPORTANCE
Autonomous parvoviruses, which possess compact genomes, are obligate intracellular parasites that necessitate host cell division for their replication cycle. Consequently, the modulation of host translation and usurpation of cellular machinery are hypothesized to facilitate immune evasion, enhance viral transmission, and perpetuate long-term infection. Despite the biological significance, the precise mechanisms by which autonomous parvoviruses regulate host translation remain understudied. Our study elucidates that CPV-2 infection induces a shutoff of host translation through the attenuation of mTOR phosphorylation. This mechanism may enable the virus to subvert the host immune response and engender pathogenic effects.
Unraveling dual fusion mechanisms in BmNPV GP64: critical roles of CARC motifs and signal peptide retention
Authors: Sun Luping , Xu Ying , Chen Kai , Nan Wenbin , Wang Meixian , Zhang Yiling , Hao Bifang , Huang Jinshan 
Published: November 2024

ABSTRACT

Viral membrane fusion is a critical process enabling viruses to invade host cells, driven by viral membrane fusion proteins (MFPs). Cholesterol plays a pivotal role in this process, which is essential for the infectivity of many enveloped viruses. The interaction between MFPs and cholesterol is often facilitated by specific amino acid motifs known as cholesterol recognition/interaction amino acid consensus (CRAC) motifs and reverse CARC motifs. In a previous study, we demonstrated that CRAC1 and CRAC2 in GP64 are required for Bombyx mori nucleopolyhedrovirus (BmNPV) infection. This study further investigates the role of CARC in the GP64 protein of BmNPV, revealing their complex interaction with cholesterol and the influence of signal peptide (SP) retention on viral infectivity. We identified six putative CARC motifs in GP64 and generated mutants to assess their function. Our findings show that CARC1, CARC2, CARC3, and CARC4 are indispensable for viral fusion and infection when the SP is retained, whereas only CARC2 and CARC3 remain essential after SP cleavage. In contrast, CARC1 and CARC4 are necessary for viral infection through a cholesterol-independent mechanism resulting from double mutations in the CRAC1 and CRAC2 motifs of GP64. These insights not only deepen our understanding of BmNPV GP64-mediated fusion but also highlight potential antiviral targets, underscoring the adaptability and resilience of viral fusion mechanisms.

IMPORTANCE
Understanding viral membrane fusion mechanisms is crucial for developing antiviral strategies. This study provides novel insights into the intricate roles of CARC and CRAC motifs in the GP64 protein of BmNPV, particularly their interaction with cholesterol and the influence of signal peptide retention. The discovery that certain CARC motifs are essential for cholesterol-dependent fusion, whereas others function in a cholesterol-independent context advances our understanding of viral fusion processes. These findings emphasize the potential of targeting CARC motifs for therapeutic interventions and underline the importance of cholesterol interactions in viral infections. This research not only deepens our understanding of BmNPV fusion mechanisms but also has broader implications for other enveloped viruses.
The antiviral activity of myricetin against pseudorabies virus through regulation of the type I interferon signaling pathway
Authors: Song Yizhen , Zhao Xufan , Chen Yaqin , Yu Xingyue , Su Tianli , Wang Juan , He Tingke , Yin Zhongqiong , Jia Renyong , Zhao Xinhong , Zhou Xun , Li Lixia , Zou Yuanfeng , Li Mingyue , Zhang Dongmei , Zhang Yingying , Song Xu 
Published: November 2024

ABSTRACT

The type I interferon signaling pathway constitutes a pivotal component of the innate immune response, encompassing the cGAS/STING and JAK/STAT pathways. Drugs that affect the body’s innate immune response could potentially be used as broad-spectrum antivirals. In this study, the antiviral activities of 25 flavonoids against pseudorabies virus (PRV) were tested in PK-15 cells. Eight active flavonoids were identified, with IC
50
values ranging from 23.24 to 323.09 µM. Subsequently, the regulatory effects of these flavonoids on the cGAS/STING pathway in PRV-infected cells were investigated. It was found that Myricetin significantly increased the transcriptional levels of
cGAS
,
STING
,
IRF3
, and
IFN-β
, which had been reduced by PRV infection. The regulation of the type I in

terferon signaling pathways by myricetin following PRV infection was further investigated through the production of cGAMP and the assessment of transcriptional and protein levels of pivotal genes and proteins. To confirm the activation of the innate immune response, a dual luciferase gene reporter study found that the expression of the IFN-β promoter in the myricetin-treated group was significantly elevated in a cellular model of type I interferon signaling pathway, and the contents of IFN-β were also significantly higher than those observed in the infected-untreated group in a PRV-infected mice model. Moreover, the transcriptional and protein levels of key genes and proteins in cell and mouse models exhibited analogous outcomes to those observed in PRV-infected cells. These findings suggest that myricetin can effectively activate the type I interferon signaling pathway, thereby enhancing the innate immune response during PRV infection.

IMPORTANCE

PRV, belonging to the
Herpesviridae
family, is an easily overlooked zoonotic pathogen that can threaten human health. The immunoprotective efficacy of conventional vaccines is significantly reduced due to the continuous mutation of the PRV genome, which constantly generates new viral strains. Therefore, there is a need to develop potent therapeutic drugs. PRV is capable of evading the host's natural immunity by suppressing the host's type I interferon signaling pathway, and the search for drugs that activate natural immunity can induce the body to produce type I IFN interferon and exert antiviral effects. Accordingly, the present study sought to identify active compounds from flavonoids that modulate the type I IFN interferon signaling pathway and thus inhibit the proliferation of PRV, which provides a new idea for the development of anti-PRV drugs from flavonoids that modulate the type I IFN interferon signaling pathway to enhance the body's antiviral immunity.
The characterization and structural basis of a human broadly binding antibody to HBV core protein
Authors: Yan Hu , Liu Congcong , Li Yuxiao , Tang Shilong , Guo Huimin , Zhou Bing , Fan Qing , Wang Haiyan , Ge Xiangyang , Wang Xin , Liao Xuejiao , Li Jin , Zhang Zheng , Ju Bin 
Published: November 2024

ABSTRACT

Hepatitis B virus (HBV) core protein (HBc) plays a crucial role in the virus life cycle, making it an important detection marker for HBV infection and a potential target for treatment. However, several commercially available monoclonal antibodies (mAbs) or polyclonal antibodies (pAbs) targeting HBc have certain limitations in detecting HBV across different genotypes in various biochemical assays, such as enzyme-linked immunosorbent assay, western blot, immunofluorescence assay, flow cytometry, and immune spot assay. In this study, we identified 12 human anti-HBc mAbs and evaluated their potential application in multiple biochemical assays. These mAbs mainly recognized the epitopes near residues 20–22 amino acids (a.a.) and 77–78 a.a. of HBc, demonstrating a broadly cross-genotypic activity. Notably, three Group II mAbs, named cAbA1, cAbD4, and cAbF9, displayed excellent capacities for the detection of HBV infection in all tested biochemical assays. Furthermore, we determined a 3.22 Å of cryo-electron microscopy (cryo-EM) structure of the fragment of antigen binding (Fab) of cAbD4 complexed with HBc dimer, which was the highest resolution of the structural model for Fab-HBc to date. Collectively, our findings provided excellent and reliable antibody candidates for live HBV detection and revealed the recognition mechanism and the detailed interaction information of a potent human anti-HBc mAb binding to the spike tips of HBc dimer.

IMPORTANCE
The lack of excellent detection Abs for live hepatitis B virus (HBV) infection and high-resolution structures of the Ab-HBV core protein (HBc) complex largely limited the development of HBV-related research. This study reports a panel of anti-HBc monoclonal antibodies (mAbs) with excellent capacities for detecting HBV infection in multiple biochemical assays and determines a 3.22 Å of cryo-EM structure of HBc with a potent binding mAb. These findings provide excellent and reliable detecting tools for HBV-related research and promote the understanding of the recognition mechanism of anti-HBc mAbs to HBc particles.
CDK12 antagonizes a viral suppressor of RNAi to modulate antiviral RNAi in
Drosophila
Authors: Zhang Liqin , Liang Yu , Qin Jiayu , Liu Chen , Shang Mengwei , Sun Xiaoming 
Published: November 2024

ABSTRACT

The primary antiviral immunity in insects is mediated by the RNA interference (RNAi) pathway. To counteract this antiviral RNAi response, viruses employ virulence factors known as viral suppressors of RNAi (VSR). The question of whether host factors can activate a counter-counter-defense mechanism to cope with VSR-mediated RNA silencing suppression remains unanswered. In this study, cyclin-dependent kinase 12 (CDK12) was identified to interact with B2, a VSR of Flock House virus (FHV), and the critical amino acids responsible for dsRNA binding and dimerization in B2 were essential for this interaction. Silencing of CDK12 facilitated FHV RNA accumulation only in the context of B2, not for FHVΔB2. Notably, CDK12 abrogated the RNAi suppression exerted by B2. Furthermore, the knockdown of CDK12 inhibited the production of vsiRNAs in FHV-infected
Drosophila
cells. This study revealed that CDK12 mediated a counter-counter-defense strategy against VSR, thereby enhancing antiviral RNAi immunity in
Drosophila
.

IMPORTANCE

The arms race between virus and host immunity is never-ending. This study enhances our understanding of antiviral defenses in insects by uncovering a novel counter-counter-defense mechanism against viral suppressors of RNA interference (VSRs). The RNA interference (RNAi) pathway serves as a primary antiviral response in insects, but viruses, such as Flock House virus (FHV), have evolved VSRs like B2 to disrupt this defense. Our research identifies cyclin-dependent kinase 12 (CDK12) as a critical host factor that interacts with the VSR B2. The discovery that CDK12 can counteract B2-mediated RNAi suppression and stimulate the production of viral small interfering RNAs (vsiRNAs) in FHV-infected
Drosophila
cells highlights its pivotal role in enhancing antiviral RNAi immunity. This study not only reveals a new dimension of host-virus interactions but also opens avenues for developing strategies to strengthen RNAi-based antiviral defenses.
Transcriptomic and genetic analysis reveals a Zn2Cys6 transcription factor specifically required for conidiation in submerged cultures of
Thermothelomyces thermophilus
Authors: Drescher Florian , Li Yang , Villalobos-Escobedo Jose Manuel , Haefner Stefan , Huberman Lori B. , Glass N. Louise 
Published: November 2024

ABSTRACT

Filamentous fungi are important producers of enzymes and secondary metabolites. The industrial thermophilic species,
Thermothelomyces thermophilus,
is closely related to the model fungus,
Neurospora crassa
. A critical aspect of the filamentous fungal life cycle is the production of asexual spores (conidia), which are regulated by various stimuli, including nutrient availability. Several species of fungi, including
T. thermophilus
, produce conidia under submerged fermentation conditions, which can be detrimental to product yields. In this study, transcriptional profiling of
T. thermophilus
was used to map changes during asexual development in submerged cultures, which revealed commonalities of regulation between
T. thermophilus
and
N. crassa
. We further identified a transcription factor,
res1
, whose deletion resulted in a complete loss of conidia production under fermentation conditions, but which did not affect conidiation on plates. Under fermentation conditions, the ∆
res1
deletion strain showed increased biomass production relative to the wild-type strain, indicating that the manipulation of
res1
in
T. thermophilus
has the potential to increase productivity in industrial settings. Overexpression of
res1
caused a severe growth defect and early conidia production on both plates and in submerged cultures, indicating
res1
overexpression can bypass regulatory aspects associated with conidiation on plates. Using chromatin-immunoprecipitation sequencing, we identified 35 target genes of Res1, including known conidiation regulators identified in
N. crassa
, revealing common and divergent aspects of asexual reproduction in these two species.

IMPORTANCE

Filamentous fungi, such as
Thermothelomyces thermophilus,
are important industrial species and have been harnessed in the Biotechnology industry for the production of industrially relevant chemicals and proteins. However, under fermentation conditions, some filamentous fungi will undergo a switch from mycelial growth to asexual development. In this study, we use transcriptional profiling of asexual development in
T. thermophilus
and identify a transcription factor that specifically regulates the developmental switch to the production of unwanted asexual propagules under fermentation conditions, thus altering secreted protein production. Mutations in this transcription factor Res1 result in the loss of asexual development in submerged cultures but do not affect asexual sporulation when exposed to air. The identification of stage-specific developmental regulation of asexual spore production and comparative analyses of conidiation in filamentous ascomycete species have the potential to further manipulate these species for industrial advantage.
Complete genome of
Nanosynbacter
sp. strain BB002, isolated and cultivated from a site of periodontal disease
Authors: Atkinson Celine Grace F. , Kerns Kristopher A. , Hendrickson Erik L. , He Xuesong , Bor Batbileg , McLean Jeffrey S. 
Published: November 2024

ABSTRACT

Nanosynbacter sp.
strain BB002, was isolated from the human oral cavity on its basibiont bacterial host
Actinomyces
sp. oral taxon 171 strain F0337, related to
Actinomyces oris
. As a member of the
Saccharibacteria
within the candidate phylum radiation group (CPR), its reduced genome facilitates the survival as an ultrasmall (<0.2 μm) epibiont.
Draft genome sequence of
Zygosaccharomyces siamensis
kiy1 isolated from unpasteurized honey
Authors: Iwata Kan , Minegishi Daisuke , Maeda Mayumi , Maehashi Kenji , Yoshikawa Jun 
Published: November 2024

ABSTRACT

In this study, a draft genome sequence of
Zygosaccharomyces siamensis
kiy1 isolated from unpasteurized honey in Japan was analyzed. This strain was reported to be a promising arabitol-producing strain, and this report contributes to a better understanding of arabitol production in yeasts.
Draft genomes of two
Roseibium
spp. isolated from the coral
Pachyseris speciosa
from a Singaporean reef
Authors: Tang Pei Yi Peggy , Loh Aaron An Rong , Hu Dalong , Deignan Lindsey Kane , Summers Stephen , Pereyra Joao Paulo Andre , Case Rebecca J. 
Published: November 2024

ABSTRACT

Two
Roseibium
spp. strains were isolated from skeletal macerates of the Singaporean coral
Pachyseris speciosa
at an ambient high temperature. We sequenced the genomes of SCP14 (
JBDZYH000000000
) and SCP15 (
JBDZYI000000000
), which revealed genomes containing genetic elements that play a role in coral health during thermal stress.
Genome sequences of three
Streptomyces
isolated from the soil of soybean field in Tsuruoka, Japan
Authors: Sato Ryuki , Saito Rena , Takeda Tomoki , Sasaki Nobuhiro , Yuzawa Satoshi , Saito Natsumi , Arakawa Kazuharu 
Published: November 2024

ABSTRACT

Streptomyces
are Gram-positive bacteria typically found in the soil, with very large genomes and high GC content, and are known to produce a wide range of secondary metabolites. We isolated and sequenced the genomes of three
Streptomyces
bacteria from the soil of soybean field in Tsuruoka, Japan.
The buoyancy of cryptococcal cells and its implications for transport and persistence of
Cryptococcus
in aqueous environments
Authors: Jimenez Isabel A. , Stempinski Piotr R. , Dragotakes Quigly , Greengo Seth D. , Sanchez Ramirez Lia , Casadevall Arturo 
Published: November 2024

ABSTRACT

Cryptococcus
is a genus of saprophytic fungi with global distribution. Two species complexes,
Cryptococcus neoformans
and
Cryptococcus gattii
, pose health risks to humans and animals. Cryptococcal infections result from inhalation of aerosolized spores and/or desiccated yeasts from terrestrial reservoirs such as soil and trees. More recently,
C. gattii
has been implicated in infections in marine mammals, suggesting that inhalation of cells from the air-water interface is also an important, yet understudied, mode of respiratory exposure. Based on historical records and epidemiological factors, water transport has been hypothesized to play a role in the spread of
C. gattii
from tropical to temperate environments. However, the dynamics of fungal persistence and transport in water have not been fully studied. The size of the cryptococcal capsule was previously shown to reduce cell density and increase buoyancy. Here, we demonstrate that cell buoyancy is also impacted by the salinity of the solution in which cells are suspended, with the formation of a halocline significantly slowing the rate of settling and resulting in persistence of
C. neoformans
within 1 cm of the water surface for over 60 min and
C. gattii
for 4–6 h. During the culture of three strains of
C. gattii
in yeast peptone dextrose media, we also identified aggregates of extracellular polysaccharide with complex structures, which we hypothesize from rafts that entrap cells and augment buoyancy. These findings illustrate new mechanisms by which cryptococcal cells may persist in aquatic environments, with important implications for aqueous transport and pathogen exposure.

IMPORTANCE

Cryptococcosis is a major fungal disease leading to morbidity and mortality worldwide.
Cryptococcus neoformans
is a major fungal species of public health concern, causing opportunistic systemic infections in immunocompromised patients.
Cryptococcus gattii
was traditionally a pathogenic fungus confined primarily to tropical regions, but in the 1990s, it emerged in the temperate climates of British Columbia, Canada and the Pacific Northwest of the United States. Outbreaks in these areas also led to the first host record of cryptococcosis in free-ranging cetaceans.
C. gattii
is particularly concerning as an emerging fungal pathogen due to its capacity to cause clinical disease in immunocompetent patients, its recent spread to a new ecological niche, and its higher resistance to antifungal therapies. Our research defines fungal characteristics that influence the transport of cryptococci through water and persistence of fungal cells near the water surface, improving our understanding of potential mechanisms for cryptococcal environmental transport.