bluuebunny/crossref_metadata_2025 huggingface dataset:
Active Expression of Genes for Protein Modification Enzymes in Habu Venom Glands
Authors: Isomoto Akiko , Shoguchi Eiichi , Hisata Kanako , Inoue Jun , Sun Yinrui , Inaba Kenji , Satoh Noriyuki , Ogawa Tomohisa , Shibata Hiroki
Published: April 2022

Genes encoding snake venom toxins have been studied extensively. However, genes involved in the modification and functioning of venom proteins are little known. Protobothrops is a genus of pit vipers, which are venomous and inhabit the Nansei (Southwest) islands of Japan, Taiwan China, Vietnam, Thailand, Myanmar, Nepal, Bhutan, and India. Our previous study decoded the genome of Protobothrops flavoviridis, a species endemic to the Nansei Islands, Japan, and revealed unique evolutionary processes of some venom genes. In this study, we analyzed genes that are highly expressed in venom glands to survey genes for candidate enzymes or chaperone proteins involved in toxin folding and modification. We found that, in addition to genes that encode venom proteins and ribosomal proteins, genes that encode protein disulfide isomerase (PDI) family members (orthologs of human P4HB and PDIA3), Selenoprotein M (SELENOM), and Calreticulin (CALR) are highly expressed in venom glands. Since these enzymes or chaperones are involved in protein modification and potentially possess protein folding functions, we propose that P4HB, SELENOM, CALR, and PDIA3 encode candidate enzymes or chaperones to confer toxic functions upon the venom transcriptome.
Correction: Malik et al. Integrated Tuberculosis and COVID-19 Activities in Karachi and Tuberculosis Case Notifications. Trop. Med. Infect. Dis. 2022, 7, 12
Authors: Malik Amyn A. , Hussain Hamidah , Maniar Rabia , Safdar Nauman , Mohiuddin Amal , Riaz Najam , Pasha Aneeta , Khan Salman , Kazmi Syed Saleem Hasan , Kazmi Ershad , Khowaja Saira
Published: April 2022

The authors wish to revise the second citation of reference [26] to [27] in the original article main text [...]
Time Trend Analysis of Tuberculosis Treatment While Using Digital Adherence Technologies—An Individual Patient Data Meta-Analysis of Eleven Projects across Ten High Tuberculosis-Burden Countries
Authors: de Groot Liza M. , Straetemans Masja , Maraba Noriah , Jennings Lauren , Gler Maria Tarcela , Marcelo Danaida , Mekoro Mirchaye , Steenkamp Pieter , Gavioli Riccardo , Spaulding Anne , Prophete Edwin , Bury Margarette , Banu Sayera , Sultana Sonia , Onjare Baraka , Efo Egwuma , Alacapa Jason , Levy Jens , Morales Mona Lisa L. , Katamba Achilles , Bogdanov Aleksey , Gamazina Kateryna , Kumarkul Dzhumagulova , Ekaterina Orechova-Li , Cattamanchi Adithya , Khan Amera , Bakker Mirjam I.
Published: April 2022

Worldwide, non-adherence to tuberculosis (TB) treatment is problematic. Digital adherence technologies (DATs) offer a person-centered approach to support and monitor treatment. We explored adherence over time while using DATs. We conducted a meta-analysis on anonymized longitudinal adherence data for drug-susceptible (DS) TB (n = 4515) and drug-resistant (DR) TB (n = 473) populations from 11 DAT projects. Using Tobit regression, we assessed adherence for six months of treatment across sex, age, project enrolment phase, DAT-type, health care facility (HCF), and project. We found that DATs recorded high levels of adherence throughout treatment: 80% to 71% of DS-TB patients had ≥90% adherence in month 1 and 6, respectively, and 73% to 75% for DR-TB patients. Adherence increased between month 1 and 2 (DS-TB and DR-TB populations), then decreased (DS-TB). Males displayed lower adherence and steeper decreases than females (DS-TB). DS-TB patients aged 15–34 years compared to those >50 years displayed steeper decreases. Adherence was correlated within HCFs and differed between projects. TB treatment adherence decreased over time and differed between subgroups, suggesting that over time, some patients are at risk for non-adherence. The real-time monitoring of medication adherence using DATs provides opportunities for health care workers to identify patients who need greater levels of adherence support.
Humoral Immune Response Induced by the BBIBP-CorV Vaccine (Sinopharm) in Healthcare Workers: A Cohort Study
Authors: Gómez de la Torre Juan C. , Cáceres-DelAguila José Alonso , Muro-Rojo Cecilia , De La Cruz-Escurra Nathalia , Copaja-Corzo Cesar , Hueda-Zavaleta Miguel , Arenas Siles Daniella , Benites-Zapata Vicente A
Published: April 2022

Insufficient data have been reported about the effect of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV) on the humoral response through time in healthcare workers (HCW). This retrospective cohort studied the information of 252 HCW from a private laboratory, comparing the antibody-mediated response provoked by BBIBP-CorV between HCW previously infected with SARS-CoV-2 (PI) and not previously infected (NPI), employing the Elecsys® anti-SARS-CoV-2 S and the cPass™ SARS-CoV-2 Neutralization Antibody Detection kit at intervals of 21, 90, and 180 days after vaccination. The presence of neutralizing antibodies in HCW 21 days after full vaccination was 100% in PI and 91.60% in NPI. We observed a progressive decrease in antibody levels over time in both groups. Comparing HCW PI with NPI, PI had a 10.9, 14.3, and 8.6-fold higher antibody titer with the Elecsys® anti-SARS-CoV-2 S at 21 (p < 0.001), 90 (p< 0.001) and 180 days (p < 0.001) respectively, compared to NPI. Using the percent of signal inhibition (PSI) of the antibody neutralization cPass™, HCW PI showed a level of 1.3, 2.0, and 3.1 times more antibodies, at 21 (p < 0.001), 90 (p < 0.001), and 180 days (p < 0.001) respectively, compared to NPI. We determined a progressive decrease in humoral immunity over time, particularly higher in those NPI.
Axion-like Particles Implications for High-Energy Astrophysics
Authors: Galanti Giorgio , Roncadelli Marco
Published: April 2022

We offer a pedagogical introduction to axion-like particles (ALPs) as far as their relevance for high-energy astrophysics is concerned, from a few MeV to 1000 TeV. This review is self-contained, in such a way to be understandable even to non-specialists. Among other things, we discuss two strong hints at a specific ALP that emerge from two very different astrophysical situations. More technical matters are contained in three Appendices.
NEAR: A New Station to Study Neutron-Induced Reactions of Astrophysical Interest at CERN-n_TOF
Authors: Gervino Gianpiero , Aberle Oliver , Bernardes Ana-Paula , Colonna Nicola , Cristallo Sergio , Diakaki Maria , Fiore Salvatore , Manna Alice , Massimi Cristian , Mastinu Pierfrancesco , Mengoni Alberto , Mucciola Riccardo , Musacchio González Elizabeth , Patronis Nikolas , Stamati Elisso , Vaz Pedro , Vlastou Rosa
Published: April 2022

We present NEAR, a new experimental area at the CERN-n_TOF facility and a possible setup for cross section measurements of interest to nuclear astrophysics. This was recently realized with the aim of performing spectral-averaged neutron-capture cross section measurements by means of the activation technique. The recently commissioned NEAR station at n_TOF is now ready for the physics program, which includes a preliminary benchmark of the proposed idea. Based on the results obtained by dedicated Monte Carlo simulations and calculation, a suitable filtering of the neutron beam is expected to enable measurements of Maxwellian Averaged Cross Section (MACS) at different temperatures. To validate the feasibility of these studies we plan to start the measurement campaign by irradiating several isotopes whose MACS at different temperatures have recently been or are planned to be determined with high accuracy at n_TOF, as a function of energy in the two time-of-flight measurement stations. For instance, the physical cases of 88Sr(n,γ), 89Y(n,γ), 94Zr(n,γ) and 64Ni(n,γ) are discussed. As the neutron capture on 89Y produces a pure β-decay emitter, we plan to test the possibility to perform activation measurements on such class of isotopes as well. The expected results of these measurements would open the way to challenging measurements of MACS by the activation technique at n_TOF, for rare and/or exotic isotopes of interest for nuclear astrophysics.
Methodologies to Measure the CP Structure of the Higgs Yukawa Coupling to Tau Leptons
Authors: Cardini Andrea
Published: April 2022

One of the central goals of the Large Hadron Collider has been the search, and later the study, of the Higgs boson. Its coupling structure under charge conjugation and parity (CP) symmetries has been extensively investigated as a probe for new physics. This paper presents a review of the methods collected in the literature to access the CP structure of the Yukawa coupling of the Higgs boson to tau leptons at proton colliders. A new notation is introduced to classify already existing methods, highlighting their common features and favoring the investigation of new, more performing alternatives.
How the Big Bang Ends Up Inside a Black Hole
Authors: Gaztanaga Enrique
Published: April 2022

The standard model of cosmology assumes that our Universe began 14 Gyrs (billion years) ago from a singular Big Bang creation. This can explain a vast range of different astrophysical data from a handful of free cosmological parameters. However, we have no direct evidence or fundamental understanding of some key assumptions: Inflation, Dark Matter and Dark Energy. Here we review the idea that cosmic expansion originates instead from gravitational collapse and bounce. The collapse generates a Black Hole (BH) of mass M≃5×1022M⊙ that formed 25 Gyrs ago. As there is no pressure support, the cold collapse can continue inside in free fall until it reaches atomic nuclear saturation (GeV), when is halted by Quantum Mechanics, as two particles cannot occupy the same quantum state. The collapse then bounces like a core-collapse supernovae, producing the Big Bang expansion. Cosmic acceleration results from the BH event horizon. During collapse, perturbations exit the horizon to re-enter during expansion, giving rise to the observed universe without the need for Inflation or Dark Energy. Using Ockham’s razor, this makes the BH Universe (BHU) model more compelling than the standard singular Big Bang creation.
Correction: Buompane et al. Recent Achievements of the ERNA Collaboration. Universe 2022, 8, 135
Authors: Buompane Raffaele , Di Leva Antonino , Gialanella Lucio , Imbriani Gianluca , Morales-Gallegos Lizeth , Romoli Mauro
Published: April 2022

In the original publication [...]
Constructing Landscape Ecological Security Patterns of an Ancient Capital Based on Cellular Automata Theory
Authors: Wang Xuhui , Li Jianwei , Zheng Tuo , Diao Shupeng , Zhang Xue , Tian Yunxi
Published: April 2022

Urban sprawl in developing countries changes urban land use structure and function, and threatens the sustainable development of regional ecology and security patterns of city landscapes. A new way to control urban sprawl is to develop a comprehensive landscape security plan, analyze factors influencing urban growth, optimize land use and demarcate a growth boundary. Here, we use Xi’an, China, as a case study to analyze scenarios of landscape security pattern and urban spatial control to explore urban spatial zoning. We construct a theoretical framework of a landscape security pattern to manage urban spatial expansion from the perspective of landscape security and urban smart growth. As a first step, the integrated landscape security pattern is constructed based on four factors: hydrology, geological disasters, cultural heritage, and recreation. Second, the urban spatial expansion model is simulated based on a cellular automata model. Finally, nine land-use patterns are developed by overlaying integrated landscape security patterns and urban spatial expansion. Thus, urban space is divided into three types of zoning scenarios: suitable construction, restricted construction, and prohibited construction. The calculations indicate that the zoning area of the three types accounted for 10.4%, 14.7%, and 74.9%, respectively, of the total area in Xi’an. It is of great significance to determine the spatial contradiction between development and protection in the process of urban expansion and to establish a schema of suitable urban land use. We discuss the rapid urbanization process in developing countries at the macro scale, and formulate a land use plan that balances development and protection.
Recognition and Evaluating the Indicators of Urban Resilient by Using the Network Analysis Process
Authors: Abedini Asghar , Aram Farshid , Khalili Amin , Mirzaei Elham
Published: April 2022

Today’s cities are increasing their space zones while becoming more vulnerable to natural disasters and man-made threats. The initial evaluation of the resilience of city systems is of great importance and helps develop policies and measures that would improve resilience. This paper, using a descriptive–analytic method, defines the characteristics of a resilient city, and natural disasters are addressed. At the same time, the process of reaching a resilient city is investigated. Then, the indicators of resilience have been defined in pillars of ecologic, physiological, social, economic, and managerial–institutional dimensions for the evaluation of a resilient city in Iran. As the sample of the study, the indicators of the study were evaluated in the city of Sanandaj and prioritized in the network analysis process (ANP). The results of this analysis showed that zones one and two, respectively, were the weakest parts regarding urban resilience. In order to move toward a resilient city, future investments should go beyond financial investment and technical solutions and consider human and community development, as well as institutional capacity and inter-organizational cooperation.
Single-Stage Trans-Vestibular and Foley’s-Assisted Epispadias Repair (STAFER) for Girls with Incontinent Epispadias: A Retrospective Study from a Tertiary-Care Center
Authors: Bajpai Minu , Anand Sachit , Goel Prabudh
Published: April 2022

Objective: The aim of this study was to evaluate the outcomes of single-stage trans-vestibular and Foley’s assisted epispadias repair (STAFER) technique in girls with incontinent epispadias. Methods: The records of all girls who had undergone epispadias repair and bladder neck plication via the STAFER technique over a four-year study period (January 2016 to December 2019) were retrospectively reviewed from the archives. A comparison of preoperative and postoperative functional outcomes was performed. Incontinence status was divided into four grades on the basis of severity: grade 0 (completely dry during day and night), grade 1 (occasional episodes of urine leakage leading to damp undergarments or requiring pads occasionally but not daily), grade 2 (frequent episodes of urine leakage with a dry period of <3 h), and grade 3 (completely incontinent). Renal bladder ultrasound (RBUS), micturating cystourethrogram (MCUG) scan, technetium-99m diethylenetriamine pentaacetate (DTPA) scan, and technetium-99m dimercaptosuccinic acid (DMSA) scan were performed to assess the upper tract function. Results: Nine girls with average (SD) age at surgery of 7.9 (3.8) years were operated on utilizing the STAFER technique during the study period. All cases had grade 3 incontinence and normal upper tracts prior to the surgery. Postoperatively, 8/9 girls had a dry period of more than 3 h. Six of them were completely dry and had no wetting episodes (grade 0 incontinence). DMSA and DTPA scans showed preserved upper tracts while MCUG scans revealed grade II VUR in only one case. Conclusions: In a limited cohort of girls with incontinent epispadias, the STAFER technique provides favorable functional outcomes in terms of continence and upper tract function. Further studies comprising a larger cohort of patients with a younger average age at surgery need to be conducted before definite conclusions regarding the efficacy of this technique are drawn.
Rational Design of a Skin- and Neuro-Attenuated Live Varicella Vaccine: A Review and Future Perspectives
Authors: Wang Wei , Pan Dequan , Cheng Tong , Zhu Hua
Published: April 2022

Primary varicella-zoster virus (VZV) infection causes varicella, which remains a prominent public health concern in children. Current varicella vaccines adopt the live-attenuated Oka strain, vOka, which retains the ability to infect neurons, establish latency and reactivate, leading to vaccine-associated zoster in some vaccinees. Therefore, it is necessary to develop a safer next-generation varicella vaccine to help reduce vaccine hesitancy. This paper reviews the discovery and identification of the skin- and neuro-tropic factor, the open reading frame 7 (ORF7) of VZV, as well as the development of a skin- and neuro-attenuated live varicella vaccine comprising an ORF7-deficient mutant, v7D. This work could provide insights into the research of novel virus vaccines based on functional genomics and reverse genetics.
Post-COVID-19 Impairment of the Senses of Smell, Taste, Hearing, and Balance
Authors: Ludwig Sonja , Schell Angela , Berkemann Michelle , Jungbauer Frederic , Zaubitzer Lena , Huber Lena , Warken Christian , Held Valentin , Kusnik Alexander , Teufel Andreas , Ebert Matthias , Rotter Nicole
Published: April 2022

Background: Various symptoms have been associated with COVID-19, but little is known about the impacts of COVID-19 on the sensory system, risk factors, and the duration of symptoms. This study assesses olfactory, gustatory, hearing, and vestibular systems after COVID-19. Methods: This cross-sectional, single-center study involved 50 patients one to six months after COVID-19 and reports their patient records and the extent, onset, and duration of olfactory, gustatory, hearing, and balance disorders using questionnaires during and after COVID-19. Sensory symptoms were objectively studied using the following clinical tests after COVID-19 Sniffin’ Sticks, taste tests, tone/speech audiometry, and video head impulse test. Results: Post-COVID-19-patients were suffering from olfactory and gustatory impairment for up to six months. According to the Dizziness Handicap Inventory, balance disorders were less noticed: Overall, about 40% of the patients during COVID-19 and nearly all patients recovered within six months. After COVID-19, clinical tests revealed that 75% were suffering from hyposomnia/anosmia, and 20% of all patients reported mild hypogeusia for up to six months. Vestibular disorders and hearing impairment rarely/did not occur. Females were significantly more affected by sensory impairments than males. Conclusions: COVID-19 particularly caused olfactory and gustatory impairment; balance disorders were present too; vestibular and auditory symptoms were negligible.
Excretion of Cell-Free and Cell-Associated Zika Virus into Breast Milk of Infected Dams and Identification of Antiviral Factors
Authors: Desgraupes Sophie , Jeannin Patricia , Gessain Antoine , Ceccaldi Pierre-Emmanuel , Vidy Aurore
Published: April 2022

Zika virus (ZIKV) is a mosquito-borne RNA virus belonging to the Flavivirus genus of the Flaviviridae family. During the 60 years following its discovery in 1947, ZIKV caused little concern for public health as the associated infection was reported as mostly asymptomatic or inducing mild symptoms. However, since 2013, severe neurological symptoms have been associated with ZIKV infection, compelling the World Health Organization to declare a Public Health Emergency of International Concern. Among those symptoms, neurological birth defects may affect children born to mothers infected during pregnancy. Additionally, during the past 8 years, ZIKV transmission through breastfeeding has repeatedly been suggested in epidemiological studies and demonstrated on a mouse model by our team. To better understand the biological factors controlling ZIKV transmission through breastfeeding, we investigated the nature of the viral entities excreted in the breast milk of infected dams and evaluated viral transmission to breastfed pups. We show that both cell-free and cell-associated virus is excreted into breast milk and that ZIKV is efficiently transmitted to the breastfed pups. Additionally, we studied murine breast milk cell types, and identified a majority of mammary luminal cells. Finally, we investigated the effect on ZIKV infectivity of several breast milk components that are antiviral against different viruses such as lactoferrin (LF) and lactalbumin (LA), or free fatty acids (FFA). We showed no effect of LF and LA, whereas FFA inactivated the virus. These results bring new insight concerning the mechanisms of ZIKV transmission during breastfeeding and identify biological factors modulating it. These elements should be considered in risk assessment of ZIKV mother-to-child transmission.
Infection with IBV DMV/1639 at a Young Age Leads to Increased Incidence of Cystic Oviduct Formation Associated with False Layer Syndrome
Authors: Mueller Slay Adrea , Franca Monique , Jackwood Mark , Jordan Brian
Published: April 2022

Infectious bronchitis virus (IBV) is an avian coronavirus that causes respiratory disease but can affect the reproductive tract of laying-type chickens. If infection occurs in pullets, false layer syndrome, which is characterized by the development of large, fluid-filled cystic oviducts, can occur. Recently, IBV strain DMV/1639 has been detected in parts of Canada and the U.S., where false layer syndrome has occurred, though it is not clear if IBV is the sole cause or if age at infection is an influencing variable. Our study investigates the role and timing of IBV infection on the development of false layer syndrome, using the IBV types DMV/1639 and Massachusetts (Mass). Six groups of 120 SPF chickens were challenged at either three, seven, or fourteen days of age, using either DMV/1639 or Mass IBV. Cystic oviducts were seen in all the challenged groups, and the pullets challenged at 14 days of age had fewer cystic oviducts than pullets challenged at 3 or 7 days of age. The highest percentage of severe histology lesion scores were seen in the 3-day challenge groups. The data collected in this experiment confirm that IBV DMV/1639 causes cystic oviducts and indicate that age at infection plays a role in the pathogenesis of false layer syndrome.
Recent Zoonotic Spillover and Tropism Shift of a Canine Coronavirus Is Associated with Relaxed Selection and Putative Loss of Function in NTD Subdomain of Spike Protein
Authors: Zehr Jordan D. , Pond Sergei L. Kosakovsky , Martin Darren P. , Ceres Kristina , Whittaker Gary R. , Millet Jean K. , Goodman Laura B. , Stanhope Michael J.
Published: April 2022

A canine coronavirus (CCoV) has now been reported from two independent human samples from Malaysia (respiratory, collected in 2017–2018; CCoV-HuPn-2018) and Haiti (urine, collected in 2017); these two viruses were nearly genetically identical. In an effort to identify any novel adaptations associated with this apparent shift in tropism we carried out detailed evolutionary analyses of the spike gene of this virus in the context of related Alphacoronavirus 1 species. The spike 0-domain retains homology to CCoV2b (enteric infections) and Transmissible Gastroenteritis Virus (TGEV; enteric and respiratory). This domain is subject to relaxed selection pressure and an increased rate of molecular evolution. It contains unique amino acid substitutions, including within a region important for sialic acid binding and pathogenesis in TGEV. Overall, the spike gene is extensively recombinant, with a feline coronavirus type II strain serving a prominent role in the recombinant history of the virus. Molecular divergence time for a segment of the gene where temporal signal could be determined, was estimated at around 60 years ago. We hypothesize that the virus had an enteric origin, but that it may be losing that particular tropism, possibly because of mutations in the sialic acid binding region of the spike 0-domain.
The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice
Authors: Hu Longbo , Xu Yuhua , Wu Liping , Feng Jin , Zhang Lu , Tang Yongjie , Zhao Xiang , Mai Runming , Chen Liyun , Mei Lingling , Tan Yuanzhen , Du Yingying , Zhen Yanping , Su Wenhan , Peng Tao
Published: April 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P- and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses.
Complexity of Human Cytomegalovirus Infection in South African HIV-Exposed Infants with Pneumonia
Authors: Govender Kerusha , Parboosing Raveen , Camiolo Salvatore , Hubáček Petr , Görzer Irene , Puchhammer-Stöckl Elisabeth , Suárez Nicolás M.
Published: April 2022

Human cytomegalovirus (HCMV) can cause significant end-organ diseases such as pneumonia in HIV-exposed infants. Complex viral factors may influence pathogenesis including: a large genome with a sizeable coding capacity, numerous gene regions of hypervariability, multiple-strain infections, and tissue compartmentalization of strains. We used a whole genome sequencing approach to assess the complexity of infection by comparing high-throughput sequencing data obtained from respiratory and blood specimens of HIV-exposed infants with severe HCMV pneumonia with those of lung transplant recipients and patients with hematological disorders. There were significantly more specimens from HIV-exposed infants showing multiple HCMV strain infection. Some genotypes, such as UL73 G4B and UL74 G4, were significantly more prevalent in HIV-exposed infants with severe HCMV pneumonia. Some genotypes were predominant in the respiratory specimens of several patients. However, the predominance was not statistically significant, precluding firm conclusions on anatomical compartmentalization in the lung.
Comprehensive Surveillance of Virus Infection among Captive African Pygmy Hedgehogs in Japan
Authors: Koizumi Iori , Tsukada Hina , Hayasaka Daisuke , Shimoda Hiroshi
Published: April 2022

African pygmy hedgehogs (Atelerix albiventris) are popular exotic pets in Japan, and their breeding numbers have recently increased. Although various diseases have been reported in hedgehogs, including skin, respiratory, neurological, and neoplastic diseases, most of the causes remain unidentified. In this study, we investigated herpesvirus, adenovirus, and coronavirus infections among 150 African pygmy hedgehogs in Japan and evaluated the correlations between virus infection and diseases. A novel herpesvirus named Atelerix albiventris herpesvirus 1 (AAHeV), and African pygmy hedgehog adenovirus 1 (AhAdV-1) were detected in 14 and 3 oral swab samples, respectively. AAHeV infection may be related to neurological clinical signs. Interestingly, no hedgehog with a neoplastic disorder tested positive for AAHeV. Further research is required to determine the pathogenicity and prevalence of the detected viruses.
Role of Feline Coronavirus as Contributor to Diarrhea in Cats from Breeding Catteries
Authors: Felten Sandra , Klein-Richers Ute , Unterer Stefan , Bergmann Michèle , Leutenegger Christian M. , Pantchev Nikola , Balzer Jörg , Zablotski Yury , Hofmann-Lehmann Regina , Hartmann Katrin
Published: April 2022

(1) Background: Feline coronavirus infection (FCoV) is common in multi-cat environments. A role of FCoV in causing diarrhea is often assumed, but has not been proven. The aim of this study was to evaluate an association of FCoV infection with diarrhea in multi-cat environments. (2) Methods: The study included 234 cats from 37 catteries. Fecal samples were analyzed for FCoV RNA by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Potential co-infections were determined by applying a qPCR panel on different potential enteropathogens and fecal flotation. A fecal scoring system was used to categorize feces as diarrheic or non-diarrheic. (3) Results: Of the 234 cats included, 23 had diarrhea. The prevalence of FCoV infection was 87.0% in cats with and 58.8% in cats without diarrhea. FCoV infection was significantly associated with diarrhea (Odds Ratio (OR) 5.01; p = 0.008). In addition, presence of Clostridium perfringens α toxin (OR 6.93; p = 0.032) and feline panleukopenia virus (OR 13.74; p = 0.004) were associated with an increased risk of diarrhea. There was no correlation between FCoV load and fecal score. FCoV-positive cats with co-infections were not more likely to have diarrhea than FCoV-positive cats without co-infections (p = 0.455). (4) Conclusions: FCoV infection is common in cats from catteries and can be associated with diarrhea.
Montelukast Inhibits HCoV-OC43 Infection as a Viral Inactivator
Authors: Chen Yongkang , Wang Xiaohuan , Shi Huichun , Zou Peng
Published: April 2022

Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the infection of HCoV-OC43 in distinct cells in a dose- and time- dependent manner. Additionally, the results showed that montelukast induced release of HCoV-OC43 genomic RNA by disrupting the integrity of the viral lipid membrane, and irreversibly inhibited viral infection. Considering the similarity among HCoV-OC43, MERS-CoV, and SARS-CoV-2, it suggests that montelukast may be a potential candidate for the treatment of human beta-coronavirus infection.
Fraternal Twins: The Enigmatic Role of the Immune System in Alphaherpesvirus Pathogenesis and Latency and Its Impacts on Vaccine Efficacy
Authors: Rouse Barry T. , Schmid D. Scott
Published: April 2022

Although the establishment, maintenance and reactivation from alphaherpesvirus latency is far from fully understood, some things are now manifestly clear: Alphaherpesvirus latency occurs in neurons of the peripheral nervous system and control of the process is multifactorial and complex. This includes components of the immune system, contributions from non-neuronal cells surrounding neurons in ganglia, specialized nucleic acids and modifications to the viral DNA to name some of the most important. Efficacious vaccines have been developed to control both acute varicella and zoster, the outcome of reactivation, but despite considerable effort vaccines for acute herpes simplex virus (HSV) infection or reactivated lesions have thus far failed to materialize despite considerable effort. Given the relevance of the immune system to establish and maintain HSV latency, a vaccine designed to tailor the HSV response to maximize the activity of components most critical for controlling reactivated infection might limit the severity of recurrences and hence reduce viral transmission. In this review, we discuss the current understanding of immunological factors that contribute to HSV and VZV latency, identify differences between varicella-zoster virus (VZV) and HSV that could explain why vaccines have been valuable at controlling VZV disease but not HSV, and finish by outlining possible strategies for developing effective HSV vaccines.
Comparative Proteomic Analysis Reveals Mx1 Inhibits Senecavirus A Replication in PK-15 Cells by Interacting with the Capsid Proteins VP1, VP2 and VP3
Authors: Gao Hang , Xiang Zhaoying , Ge Xinna , Zhou Lei , Han Jun , Guo Xin , Chen Yanhong , Zhang Yongning , Yang Hanchun
Published: April 2022

As an emergent picornavirus pathogenic to pigs, Senecavirus A (SVA) can replicate in pig kidneys and proliferates well in porcine kidney epithelial PK-15 cells. Here, tandem mass tags (TMT) labeling coupled with liquid chromatography–tandem mass spectrometry (LC-MS/MS) was used to analyze the proteome dynamic changes in PK-15 cells during SVA infection. In total, 314, 697 and 426 upregulated differentially expressed proteins (DEPs) and 131, 263 and 342 downregulated DEPs were identified at 12, 24 and 36 hpi, respectively. After ensuring reliability of the proteomic data by quantitative PCR and Western blot testing of five randomly selected DEPs, Mx1, eIF4E, G6PD, TOP1 and PGAM1, all the DEPs were subjected to multiple bioinformatics analyses, including GO, COG, KEGG and STRING. The results reveal that the DEPs were mainly involved in host innate and adaptive immune responses in the early and middle stages of SVA infection, while the DEPs mainly participated in various metabolic processes in the late stage of infection. Finally, we demonstrated that Mx1 protein exerts antiviral activity against SVA by interacting with VP1 and VP2 proteins dependent on its GTPase, oligomerization and interaction activities, while Mx1 interacts with VP3 only depending on its oligomerization activity. Collectively, our study provides valuable clues for further investigation of SVA pathogenesis.
Early-Life Colonization by Anelloviruses in Infants
Authors: Kaczorowska Joanna , Cicilionytė Aurelija , Timmerman Anne L. , Deijs Martin , Jebbink Maarten F. , van Goudoever Johannes B. , van Keulen Britt J. , Bakker Margreet , van der Hoek Lia
Published: April 2022

Anelloviruses (AVs) are found in the vast majority of the human population and are most probably part of a healthy virome. These viruses infect humans in the early stage of life, however, the characteristics of the first colonizing AVs are still unknown. We screened a collection of 107 blood samples from children between 0.4 and 64.8 months of age for the presence of three AV genera: the Alpha-, Beta- and Gammatorquevirus. The youngest child that was positive for AV was 1.2 months old, and a peak in prevalence (100% of samples positive) was reached between the twelfth and eighteenth months of life. Intriguingly, the beta- and gammatorqueviruses were detected most at the early stage of life (up to 12 months), whereas alphatorqueviruses, the most common AVs in adults, increased in prevalence in children older than 12 months. To determine whether that order of colonization may be related to oral transmission and unequal presence of AV genera in breast milk, we examined 63 breast milk samples. Thirty-two percent of the breast milk samples were positive in a qPCR detecting beta- and gammatorqueviruses, while alphatorqueviruses were detected in 10% of the samples, and this difference was significant (p = 0.00654). In conclusion, we show that beta- and gammatorqueviruses colonize humans in the first months of life and that breastfeeding could play a role in AV transmission.
The Effect of Zero-Valent Iron Nanoparticles (nZVI) on Bacteriophages
Authors: Raza Sada , Folga Michał , Łoś Marcin , Foltynowicz Zenon , Paczesny Jan
Published: April 2022

Bacteriophages are viruses that attack and usually kill bacteria. Their appearance in the industrial facilities using bacteria to produce active compounds (e.g., drugs, food, cosmetics, etc.) causes considerable financial losses. Instances of bacteriophage resistance towards disinfectants and decontamination procedures (such as thermal inactivation and photocatalysis) have been reported. There is a pressing need to explore new ways of phage inactivation that are environmentally neutral, inexpensive, and more efficient. Here, we study the effect of zero-valent iron nanoparticles (nZVI) on four different bacteriophages (T4, T7, MS2, M13). The reduction of plaque-forming units (PFU) per mL varies from greater than 7log to around 0.5log depending on bacteriophages (M13 and T7, respectively). A comparison of the importance of oxidation of nZVI versus the release of Fe2+/Fe3+ ions is shown. The mechanism of action is proposed in connection to redox reactions, adsorption of virions on nZVI, and the effect of released iron ions. The nZVI constitutes a critical addition to available antiphagents (i.e., anti-bacteriophage agents).
Early and Longitudinal Humoral Response to the SARS-CoV-2 mRNA BNT162b2 Vaccine in Healthcare Workers: Significance of BMI, Adipose Tissue and Muscle Mass on Long-Lasting Post-Vaccinal Immunity
Authors: Golec Marlena , Fronczek Martyna , Zembala-John Joanna , Chrapiec Martyna , Konka Adam , Wystyrk Karolina , Botor Hanna , Brzoza Zenon , Kasperczyk Sławomir , Bułdak Rafał Jakub
Published: April 2022

Background: This study aimed to investigate the early and longitudinal humoral response in Healthcare Workers (HCWs) after two doses of the BNT162b2 vaccine and to assess the association between metabolic and anthropometric parameters and the humoral response after vaccination. Methods: The study included 243 fully vaccinated HCWs: 25.50% previously infected with SARS-CoV-2 (with prior history of COVID-19—PH) and 74.40%—uninfected, seronegative before the first vaccination (with no prior history of COVID-19—NPH). IgG antibodies were measured, and sera were collected: prior to the vaccination, 21 days after the first dose, and 14 days and 8 months after the second dose. Results: 21 days after the first dose, 90.95% of individuals were seropositive; 14 days after the second dose, persistent immunity was observed in 99.18% HCWs, 8 months after complete vaccination—in 61.73%. Statistical analysis revealed that HCWs with PH had a greater chance of maintaining a humoral response beyond eight months after vaccination. Increased muscle mass, decreased fat mass, and younger age may positively affect long-term immunity. Smokers have a reduced chance of developing immunity compared to non-smokers. Conclusions: Fully vaccinated HCWs with PH are more likely to be seropositive than fully inoculated volunteers with NPH.
Efficacy of an HSV-1 Neuro-Attenuated Vaccine in Mice Is Reduced by Preventing Viral DNA Replication
Authors: Wang Hong , Davido David J. , Mostafa Heba H. , Morrison Lynda A.
Published: April 2022

We previously isolated an HSV-1 mutant, KOS-NA, that contains two non-synonymous mutations in UL39. One of the mutations, resulting in an R950H amino acid substitution in ICP6, renders KOS-NA severely neuro-attenuated and significantly reduces HSV-1 latency. Vaccination of mice with KOS-NA prior to corneal challenge provides significant protection against HSV-1-mediated eye diseases even at a very low immunizing dose, indicating its utility as a vaccine scaffold. Because KOS-NA contains a neuro-attenuating mutation in a single gene, we sought to improve its safety by deleting a portion of the UL29 gene whose protein product, ICP8, is essential for viral DNA replication. Whereas KOS-NA reduced replication of HSV-1 challenge virus in the corneal epithelium and protected mice against blepharitis and keratitis induced by the challenge virus, KOS-NA/8- and an ICP8- virus were significantly less efficacious except at higher doses. Our results suggest that the capacity to replicate, even at significantly reduced levels compared with wild-type HSV-1, may be an important feature of an effective vaccine. Means to improve safety of attenuated viruses as vaccines without compromising efficacy should be sought.
First Report of TTSuV1 in Domestic Swiss Pigs
Authors: Polster Sabrina , Lechmann Julia , Lienhard Julia , Peltzer Deborah , Prähauser Barbara , Bachofen Claudia , Seehusen Frauke
Published: April 2022

Serum prevalence of Torque teno sus viruses (TTSuV1 and k2; family Anelloviridae) is known to be high in the porcine population worldwide but pathogenesis and associated pathomorphological lesions remain to be elucidated. In this study, quantitative real-time PCR for detection of TTSuV1 was performed in 101 porcine samples of brain tissue, with animals showing inflammatory lesions or no histological changes. Additionally, a pathomorphological and immunohistochemical characterization of possible lesions was carried out. Selected cases were screened by TTSuV1 in situ hybridization. Furthermore, TTSuV1 quantitative real-time PCR in splenic and pulmonary tissue and in situ hybridization (ISH) in spleen, lungs, mesenteric lymph node, heart, kidney, and liver were performed in 22 animals. TTSuV1 was detected by PCR not only in spleen and lung but also in brain tissue (71.3%); however, in general, spleen and lung tissue displayed lower Ct values than the brain. Positive TTSuV1 results were frequently associated with the morphological diagnosis of non-suppurative encephalitis. Single TTSuV1-positive lymphocytes were detected by ISH in the brain but also in lungs, spleen, mesenteric lymph node and in two cases of non-suppurative myocarditis. A pathogenetic role of a TTSuV1 infection as a co-factor for non-suppurative encephalitides cannot be ruled out.
Surveillance of Viral Encephalitis in the Context of COVID-19: A One-Year Observational Study among Hospitalized Patients in Dakar, Senegal
Authors: Kahwagi Jamil , Seye Al Ousseynou , Mbodji Ahmadou Bamba , Diagne Rokhaya , Mbengue El hadji , Fall Maouly , Andriamandimby Soa Fy , Easton Ava , Faye Martin , Fall Gamou , Dia Ndongo , Ndiaye Babacar , Ndiaye Momo Banda , Gueye Alle , Mbacke Serigne Saliou , Kane Fatou , Ghouriechy Mohamed Inejih ,   ENSENE Investigators, Seck Lala Bouna , Gaye Ndiaga Matar , Sall Amadou Alpha , Ndiaye Moustapha , Faye Ousmane , Diop Amadou Gallo , Heraud Jean-Michel
Published: April 2022

The burden of encephalitis and its associated viral etiology is poorly described in Africa. Moreover, neurological manifestations of COVID-19 are increasingly reported in many countries, but less so in Africa. Our prospective study aimed to characterize the main viral etiologies of patients hospitalized for encephalitis in two hospitals in Dakar. From January to December 2021, all adult patients that met the inclusion criteria for clinical infectious encephalitis were enrolled. Cerebrospinal fluids, blood, and nasopharyngeal swabs were taken and tested for 27 viruses. During the study period, 122 patients were enrolled. Viral etiology was confirmed or probable in 27 patients (22.1%), with SARS-CoV-2 (n = 8), HSV-1 (n = 7), HHV-7 (n = 5), and EBV (n = 4) being the most detected viruses. Age groups 40–49 was more likely to be positive for at least one virus with an odds ratio of 7.7. The mortality was high among infected patients, with 11 (41%) deaths notified during hospitalization. Interestingly, SARS-CoV-2 was the most prevalent virus in hospitalized patients presenting with encephalitis. Our results reveal the crucial need to establish a country-wide surveillance of encephalitis in Senegal to estimate the burden of this disease in our population and implement strategies to improve care and reduce mortality.
Mass Spectrometry Approaches for SARS-CoV-2 Detection: Harnessing for Application in Food and Environmental Samples
Authors: Bojórquez-Velázquez Esaú , Llamas-García Miriam Livier , Elizalde-Contreras José M. , Zamora-Briseño Jesús Alejandro , Ruiz-May Eliel
Published: April 2022

The public health crisis caused by the emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in 2019 has drastically changed our lifestyle in virtually all contexts around the world. SARS-CoV-2 is mainly airborne, transmitted by the salivary droplets produced when infected people cough or sneeze. In addition, diarrhea symptoms and the detection of SARS-CoV-2 in feces suggest a fecal–oral route of contagion. Currently, the high demand for SARS-CoV-2 diagnosis has surpassed the availability of PCR and immunodetection probes and has prompted the development of other diagnostic alternatives. In this context, mass spectrometry (MS) represents a mature, robust alternative platform for detection of SARS-CoV-2 and other human viruses. This possibility has raised great interest worldwide. Therefore, it is time for the global application of MS as a feasible option for detecting SARS-CoV-2, not only in human fluids, but also in other matrices such as foods and wastewater. This review covers the most relevant established methods for MS-based SARS-CoV-2 detection and discusses the future application of these tools in different matrices. Significance: The Coronavirus Disease 2019 (COVID-19) pandemic highlighted the pros and cons of currently available PCR and immunodetection tools. The great concern over the infective potential of SARS-CoV-2 viral particles that can persist for several hours on different surfaces under various conditions further evidenced the need for reliable alternatives and high-throughput methods to meet the needs for mass detection of SARS-CoV-2. In this context, MS-based proteomics emerging from fundamental studies in life science can offer a robust option for SARS-CoV-2 detection in human fluids and other matrices. In addition, the substantial efforts towards detecting SARS-CoV-2 in clinal samples, position MS to support the detection of this virus in different matrices such as the surfaces of the packing food process, frozen foods, and wastewaters. Proteomics and mass spectrometry are, therefore, well positioned to play a role in the epidemiological control of COVID-19 and other future diseases. We are currently witnessing the opportunity to generate technologies to overcome prolonged pandemics for the first time in human history.