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Arch Virol 2021 Jul 20;166(7):1869-1875. Epub 2021 Apr 20.

Department of Virology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Academician Georgi Bonchev Street, 1113, Sofia, Bulgaria.

Although chemotherapy is generally indicated for treatment of enterovirus infections, antivirals are currently not used in clinical practice. The use of monotherapy is the main reason for this unfavourable state. This is related to the fact that enterovirus progeny consist of innumerable quasispecies, allowing the virus to develop drug resistance quickly. Read More

J Virol 2021 05 24;95(12). Epub 2021 May 24.

Centre for Heart and Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada

During viral infection, the dynamic virus-host relationship is constantly in play. Many cellular proteins, such as RNA-binding proteins (RBPs), have been shown to mediate antiviral responses during viral infection. Here, we report that the RBP FUS/TLS (fused in sarcoma/translocated in liposarcoma) acts as a host-restricting factor against infection with coxsackievirus B3 (CVB3). Read More

Acta Virol 2021 ;65(1):58-67

Coxsackie virus B3 (CVB3) is believed to be a major cause of viral myocarditis, with virus-induced apoptosis playing an important role in pathogenesis. The purpose of this study was to characterize the antiviral activity of a novel fluoronucleoside analogue, N-cyclopropyl-4'-azido-2'-deoxy-2'-fluoro-β-D-cytidine (NCC), against CVB3 in vitro and in vivo, and to establish whether NCC inhibits apoptosis in infected cells. In this study, HeLa cells infected with CVB3 were treated with NCC. Read More

Viruses 2021 03 31;13(4). Epub 2021 Mar 31.

Laboratório de Diversidade Viral, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belem 66075-000, Pará, Brazil.

Echoviruses (E) are a diverse group of viruses responsible for various pathological conditions in humans including aseptic meningitis, myocarditis, and acute flaccid paralysis. The detection and identification of echovirus genotypes in clinical samples is challenging due to its high genetic diversity. Here, we report the complete genome sequences of nine echoviruses, obtained by next-generation sequencing of 238 fecal samples from individuals with gastroenteritis in regions of Brazil. Read More

Int J Mol Sci 2021 Mar 17;22(6). Epub 2021 Mar 17.

Department of Biomedical Science, Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun, Chungbuk 28024, Korea.

Coxsackievirus and adenovirus receptor (CAR) is present in epithelial and vascular endothelial cell junctions. We have previously shown a hemorrhagic phenotype in germ-line CAR knock-out mouse embryos; we have also found that CAR interacts with ZO-1 and β-catenin. However, the role of CAR in vascular endothelial junction permeability has not been proven. Read More

J Virol 2021 05 24;95(12). Epub 2021 May 24.

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China

Enteroviruses belong to the genus of the family and include four human enterovirus groups (EV-A to -D): the epidemic of enteroviruses such as human enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16) is a threat to global public health. Enteroviral protein 2C is the most conserved nonstructural protein among all enteroviruses and possesses RNA helicase activity that plays pivotal roles during enteroviral life cycles, which makes 2C an attractive target for developing antienterovirus drugs. In this study, we designed a peptide, named 2CL, based on the structure of EV-A71 2C. Read More

Biomed Environ Sci 2020 Nov;33(11):829-838

The School of Public Health, Fujian Medical University, Fuzhou 350122, Fujian, China.

Objective: To develop RT-nPCR assays for amplifying partial and complete VP1 genes of human enteroviruses (HEVs) from clinical samples and to contribute to etiological surveillance of HEV-related diseases.

Methods: A panel of RT-nPCR assays, consisting of published combined primer pairs for VP1 genes of HEV A-C and in-house designed primers for HEV-D, was established in this study. The sensitivity of each RT-nPCR assay was evaluated with serially diluted virus stocks of five serotypes expressed as CCID per μL and copies per μL, and the newly established methods were tested in clinical specimens collected in recent years. Read More

Int Immunopharmacol 2021 Jun 19;95:107534. Epub 2021 Mar 19.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address:

Background: The aim of this study was to investigate the mechanism of STAT3 in reducing the inflammatory responses in mice with viral myocarditis (VMC).

Methods: Induce and generate viral myocarditis by using coxsackievirus B3 (CVB3) infected cardiomyocyte-specific STAT3 conditional knockout (STAT3cKO) mice and BALB/c mice. Use RT-PCR and western blot techniques to detect the expression of related cytokines in the uninfected wild-type mice group (Control group), myocarditis wild-type mice group (Model group) and STAT3cKO group, as well as the differentiation of spleen T cells in each group. Read More

Arch Virol 2021 May 26;166(5):1305-1312. Epub 2021 Feb 26.

Medical School, Anhui University of Science and Technology, Huainan, 232001, Anhui, People's Republic of China.

Echovirus 6 (E6) is associated with various clinical diseases and is frequently detected in environmental sewage. Despite its high prevalence in humans and the environment, little is known about its molecular phylogeography in mainland China. In this study, 114 of 21,539 (0. Read More

Environ Sci Technol 2021 03 15;55(5):3156-3164. Epub 2021 Feb 15.

Department of Urban Engineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654, Japan.

The disinfection susceptibilities of viruses vary even among variants, yet the inactivation efficiency of a certain virus genotype, species, or genus was determined based on the susceptibility of its laboratory strain. The objectives were to evaluate the variability in susceptibilities to free chlorine, UV, and ozone among 13 variants of coxsackievirus B5 (CVB5) and develop the model allowing for predicting the overall inactivation of heterogeneous CVB5. Our results showed that the susceptibilities differed by up to 3. Read More

PLoS Pathog 2021 02 8;17(2):e1008992. Epub 2021 Feb 8.

The First Affiliated Hospital of Nanchang University, Nanchang, China.

Coxsackievirus B3 (CVB3) belongs to the genus Enterovirus of the family Picornaviridae and can cause acute acinar pancreatitis in adults. However, the molecular mechanisms of pathogenesis underlying CVB3-induced acute pancreatitis have remained unclear. In this study, we discovered that CVB3 capsid protein VP1 inhibited pancreatic cell proliferation and exerted strong cytopathic effects on HPAC cells. Read More

Arch Virol 2021 Apr 8;166(4):1231-1236. Epub 2021 Feb 8.

Department of Pediatric Intensive Care Unit (PICU), The Affiliated Wuxi Children's Hospital of Nanjing Medical University, Wuxi, 214023, China.

The species Enterovirus B includes diverse serotypes that can cause a wide spectrum of human diseases, such as aseptic encephalitis, myocarditis, and paralysis. In this study, a 4-year-old child was diagnosed with viral encephalitis, but the causative agent could not be identified using routine immunological tests. Using metagenomic RNA sequencing, a novel strain of enterovirus B, strain PC06, was identified, and its genome sequence was determined by RT-PCR and Sanger sequencing. Read More

Viruses 2021 02 3;13(2). Epub 2021 Feb 3.

Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea.

Genetic screens using CRISPR/Cas9 have been exploited to discover host-virus interactions. These screens have identified viral dependencies on host proteins during their life cycle and potential antiviral strategies. The acyl-CoA binding domain containing 3 (ACBD3) was identified as an essential host factor for the Coxsackievirus B3 (CVB3) infection. Read More

Front Immunol 2020 14;11:603437. Epub 2021 Jan 14.

Department of Cardiothoracic Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China.

Viral myocarditis is caused by a viral infection and characterized by the inflammation of the myocardium. Coxsackievirus B3 (CVB3) infection is one of the most common among the infections caused by this virus. The host's early innate immune response to CVB3 infection particularly depends on the functions of type I interferons (IFNs). Read More

Int J Mol Sci 2021 Jan 27;22(3). Epub 2021 Jan 27.

Institute of Medical Microbiology and Virology, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.

The association of members of the enterovirus family with pregnancy complications up to miscarriages is under discussion. Here, infection of two different human induced pluripotent stem cell (iPSC) lines and iPSC-derived primary germ-layer cells with coxsackievirus B3 (CVB3) was characterized as an in vitro cell culture model for very early human development. Transcriptomic analysis of iPSC lines infected with recombinant CVB3 expressing enhanced green fluorescent protein (EGFP) revealed a reduction in the expression of pluripotency genes besides an enhancement of genes involved in RNA metabolism. Read More

PLoS Pathog 2021 01 29;17(1):e1009252. Epub 2021 Jan 29.

Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

Neonatal echovirus infections are characterized by severe hepatitis and neurological complications that can be fatal. Here, we show that expression of the human homologue of the neonatal Fc receptor (hFcRn), the primary receptor for echoviruses, and ablation of type I interferon (IFN) signaling are key host determinants involved in echovirus pathogenesis. We show that expression of hFcRn alone is insufficient to confer susceptibility to echovirus infections in mice. Read More

Anticancer Res 2021 Jan;41(1):81-89

Laboratory of ALA Advanced Medical Research, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan

Background/aim: Breast cancer is the most common cancer in women worldwide, and triple-negative breast cancer (TNBC) is highly refractory to current standard therapies. Oncolytic virotherapy has recently gathered attention as a new treatment candidate for refractory cancers.

Materials And Methods: We previously developed a new Coxsackievirus B3 (CVB3) virotherapy targeting lung cancers, and demonstrated that miRNA target sequence insertion into CVB3 reduced its pathogenicity, retaining its original oncolytic activity. Read More

Am J Physiol Heart Circ Physiol 2021 04 8;320(4):H1348-H1360. Epub 2021 Jan 8.

Department of Cardiology, the First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, People's Republic of China.

Viral myocarditis (VMC) is a life-threatening disease characterized by severe cardiac inflammation generally caused by coxsackievirus B3 (CVB3) infection. Several microRNAs (miRNAs or miRs) are known to play crucial roles in the pathogenesis of VMC. The study aimed to decipher the role of miR-30a-5p in the underlying mechanisms of VMC pathogenesis. Read More

Viruses 2020 11 20;12(11). Epub 2020 Nov 20.

National/OIE/FAO Reference Centre for Foot-and-Mouth Disease and for Swine Vesicular Disease, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna (IZSLER), via Bianchi 9, 24125 Brescia, Italy.

During the last 25 years, swine vesicular disease (SVD) has occurred in Italy mostly sub-clinically. Therefore, regular testing of fecal samples from suspected holdings and high turnover premises was fundamental to identifying virus circulation and to achieve SVD eradication. In this study, we evaluated diagnostic performances of six genomic amplification methods, using positive fecal samples from 78 different outbreaks (1997-2014), which included different lineages. Read More

Am J Trop Med Hyg 2020 11;103(5):1753

Department of Rheumatology, Tripler Army Medical Center, Honolulu, Hawaii.

J Nanosci Nanotechnol 2021 Feb;21(2):1365-1371

Department of Cardiovascular Medicine, Huadu District People's Hospital, Southern Medical University, Guangzhou, 510800, China.

Micro RNA-146 (miR-146) is involved in mediating many innate and adaptive immune and inflammatory responses in the body. It is associated with a variety of systemic inflammation or autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and type 2 diabetes. In recent years, microRNAs (miRNAs) and nanotechnology have become research hotspots in cardiovascular pathology. Read More

Int Immunopharmacol 2020 Nov 12;88:106941. Epub 2020 Sep 12.

Department of Children's Genetics and Infectious Diseases Laboratory, Dongguan Institute of Pediatrics, Dongguan, Guangdong 510000, China; Department of Respiratory Medicine, Dongguan Children's Hospital, Dongguan, Guangdong 510000, China. Electronic address:

Viral myocarditis (VMC) is characterized by cardiac inflammation and excessive inflammatory responses after viral infection. SENP2, a deSUMO-specific protease, has been reported to regulate antiviral innate immunity. This study aimed to investigate whether SENP2 affects CVB3-induced VMC. Read More

Viruses 2020 11 5;12(11). Epub 2020 Nov 5.

Next Generation Sequencing Unit, University of the Free State, Bloemfontein 9300, South Africa.

Establishing a diverse gut microbiota after birth is essential for preventing illnesses later in life. However, little knowledge exists about the total viral population (virome) present in the gut of infants during the early developmental stage, with RNA viruses being generally overlooked. Therefore, this small pilot longitudinal study investigated the diversity and changes in the enteric RNA virome in healthy infants from South Africa. Read More

Viruses 2020 10 30;12(11). Epub 2020 Oct 30.

Institute of Bioorganic Chemistry Polish Academy of Sciences, Zygmunta Noskowskiego 12/14, 61-704 Poznań, Poland.

Here we present a set of new structural elements formed within the open reading frame of the virus, which are highly probable, evolutionarily conserved and may interact with host proteins. This work focused on the coding regions of the CVB3 genome (particularly the V4-, V1-, 2C-, and 3D-coding regions), which, with the exception of the -acting replication element (CRE), have not yet been subjected to experimental analysis of their structures. The SHAPE technique, chemical modification with DMS and RNA cleavage with Pb, were performed in order to characterize the RNA structure. Read More

Viruses 2020 10 18;12(10). Epub 2020 Oct 18.

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, 7028 Trondheim, Norway.

Combination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify new synergistic combinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), echovirus 1 (EV1), hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1) in vitro. Read More

Viruses 2020 09 25;12(10). Epub 2020 Sep 25.

Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.

Enteroviruses manipulate host membranes to form replication organelles, which concentrate viral and host factors to allow for efficient replication. However, this process has not been well-studied in living cells throughout the course of infection. To define the dynamic process of enterovirus membrane remodeling of major secretory pathway organelles, we have developed plasmid-based reporter systems that utilize viral protease-dependent release of a nuclear-localized fluorescent protein from the endoplasmic reticulum (ER) membrane during infection, while retaining organelle-specific fluorescent protein markers such as the ER and Golgi. Read More

Nat Commun 2020 09 4;11(1):4419. Epub 2020 Sep 4.

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences and College of Pharmacy and Drug Discovery Center for Infectious Diseases, Nankai University, 300353, Tianjin, China.

Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Read More

Nat Commun 2020 09 4;11(1):4421. Epub 2020 Sep 4.

CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

Receptor usage that determines cell tropism and drives viral classification closely correlates with the virus structure. Enterovirus B (EV-B) consists of several subgroups according to receptor usage, among which echovirus 30 (E30), a leading causative agent for human aseptic meningitis, utilizes FcRn as an uncoating receptor. However, receptors for many EVs remain unknown. Read More

Environ Sci Technol 2020 09 2;54(18):11292-11300. Epub 2020 Sep 2.

Laboratory of Environmental Chemistry, School of Architecture, Civil and Environmental Engineering (ENAC), École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.

Sunlight, temperature, and microbial grazing are among the environmental factors promoting the inactivation of viral pathogens in surface waters. Globally, these factors vary across time and space. The persistence of viral pathogens, and ultimately their ecology and dispersion, hinges on their ability to withstand the environmental conditions encountered. Read More