-
Viruses Sep 2021Mumps virus (MuV) is an important human pathogen that causes parotitis, orchitis, oophoritis, meningitis, encephalitis, and sensorineural hearing loss. Although mumps is... (Review)
Review
Mumps virus (MuV) is an important human pathogen that causes parotitis, orchitis, oophoritis, meningitis, encephalitis, and sensorineural hearing loss. Although mumps is a vaccine-preventable disease, sporadic outbreaks have occurred worldwide, even in highly vaccinated populations. MuV not only causes systemic infection but also has a unique tropism to glandular tissues and the central nervous system. In general, tropism can be defined by multiple factors in the viral life cycle, including its entry, interaction with host factors, and host-cell immune responses. Although the underlying mechanisms of MuV tropism remain to be fully understood, recent studies on virus-host interactions have provided insights into viral pathogenesis. This review was aimed at summarizing the entry process of MuV by focusing on the glycan receptors, particularly the recently identified receptors with a trisaccharide core motif, and their interactions with the viral attachment proteins. Here, we describe the receptor structures, their distribution in the human body, and the recently identified host factors for MuV and analyze their relationship with MuV tropism.
Topics: Host-Pathogen Interactions; Humans; Mumps; Mumps virus; Protein Binding; Receptors, Virus; Viral Proteins; Viral Tropism; Virus Attachment; Virus Internalization
PubMed: 34578327
DOI: 10.3390/v13091746 -
Epidemiology and Infection May 2023This study aims to evaluate the impact of non-pharmaceutical interventions (NPIs) on the prevalence of respiratory pathogens among hospitalised children with acute...
This study aims to evaluate the impact of non-pharmaceutical interventions (NPIs) on the prevalence of respiratory pathogens among hospitalised children with acute respiratory infections (ARIs) in Suzhou. Children with ARIs admitted to the Children's Hospital of Soochow University between 1 September 2021 and 31 December 2022 and subjected to 13 respiratory pathogen multiplex PCR assays were included in the study. We retrospectively collected demographic details, results of respiratory pathogen panel tests, and discharge diagnostic information of the participants, and described the age and seasonal distribution of respiratory pathogens and risk factors for developing pneumonia. A total of 10,396 children <16 years of age, including 5,905 males and 4,491 females, were part of the study. The positive rates of the 11 respiratory pathogen assays were 23.3% (human rhinovirus (HRV)), 15.9% (human respiratory syncytial virus (HRSV)), 10.5% (human metapneumovirus (HMPV)), 10.3% (human parainfluenza virus (HPIV)), 8.6% (mycoplasma pneumoniae (MP)), 5.8% (Boca), 3.5% (influenza A (InfA)), 2.9% (influenza B (InfB)), 2.7% (human coronavirus (HCOV)), 2.0% (adenovirus (ADV)), and 0.5% (Ch), respectively. Bocavirus and HPIV detection peaked during the period from September to November (autumn), and MP and HMPV peaked in the months of November and December. The peak of InfA detection was found to be in summer (July and August), whereas the InfB peak was observed to be in winter (December, January, and February). HRSV and HRV predominated in the <3 years age group. HRV and HMPV were common in the 3-6 years group, whereas MP was predominant in the ≥6 years group. MP (odds ratio (OR): 70.068, 95%CI: 32.665-150.298, < 0.01), HMPV (OR: 6.493, 95%CI: 4.802-8.780, < 0.01), Boca (OR: 3.300, 95%CI: 2.186-4.980, < 0.01), and HRSV (OR: 2.649, 95%CI: 2.089-3.358, < 0.01) infections were more likely to develop into pneumonia than the other pathogens. With the use of NPIs, HRV was the most common pathogen in children with ARIs, and MP was more likely to progress to pneumonia than other pathogens.
Topics: Child; Male; Female; Humans; Influenza, Human; Prevalence; Retrospective Studies; Pneumonia; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Metapneumovirus; China
PubMed: 37127406
DOI: 10.1017/S0950268823000626 -
Viruses Mar 2022Metapneumoviruses, members of the family Pneumoviridae, have been identified in birds (avian metapneumoviruses; AMPV's) and humans (human metapneumoviruses; HMPV's).... (Review)
Review
Metapneumoviruses, members of the family Pneumoviridae, have been identified in birds (avian metapneumoviruses; AMPV's) and humans (human metapneumoviruses; HMPV's). AMPV and HMPV are closely related viruses with a similar genomic organization and cause respiratory tract illnesses in birds and humans, respectively. AMPV can be classified into four subgroups, A-D, and is the etiological agent of turkey rhinotracheitis and swollen head syndrome in chickens. Epidemiological studies have indicated that AMPV also circulates in wild bird species which may act as reservoir hosts for novel subtypes. HMPV was first discovered in 2001, but retrospective studies have shown that HMPV has been circulating in humans for at least 50 years. AMPV subgroup C is more closely related to HMPV than to any other AMPV subgroup, suggesting that HMPV has evolved from AMPV-C following zoonotic transfer. In this review, we present a historical perspective on the discovery of metapneumoviruses and discuss the host tropism, pathogenicity, and molecular characteristics of the different AMPV and HMPV subgroups to provide increased focus on the necessity to better understand the evolutionary pathways through which HMPV emerged as a seasonal endemic human respiratory virus.
Topics: Animals; Chickens; Humans; Metapneumovirus; Paramyxoviridae Infections; Poultry Diseases; Retrospective Studies
PubMed: 35458407
DOI: 10.3390/v14040677 -
Proceedings of the National Academy of... Apr 2024Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and...
Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and fusion (F) glycoproteins which are the main targets of neutralizing antibodies. We show here that the LayV F and G glycoproteins promote membrane fusion with human, mouse, and hamster target cells using a different, yet unknown, receptor than Nipah virus (NiV) and Hendra virus (HeV) and that NiV- and HeV-elicited monoclonal and polyclonal antibodies do not cross-react with LayV F and G. We determined cryoelectron microscopy structures of LayV F, in the prefusion and postfusion states, and of LayV G, revealing their conformational landscape and distinct antigenicity relative to NiV and HeV. We computationally designed stabilized LayV G constructs and demonstrate the generalizability of an HNV F prefusion-stabilization strategy. Our data will support the development of vaccines and therapeutics against LayV and closely related HNVs.
Topics: Humans; Animals; Mice; Cryoelectron Microscopy; Nipah Virus; Hendra Virus; Glycoproteins; Henipavirus Infections; Virus Internalization; Henipavirus
PubMed: 38593070
DOI: 10.1073/pnas.2314990121 -
Viruses Dec 2020The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant... (Review)
Review
The paramyxo- and pneumovirus family includes a wide range of viruses that can cause respiratory and/or systemic infections in humans and animals. The significant disease burden of these viruses is further exacerbated by the limited therapeutics that are currently available. Host cellular proteins that can antagonize or limit virus replication are therefore a promising area of research to identify candidate molecules with the potential for host-targeted therapies. Host proteins known as host cell restriction factors are constitutively expressed and/or induced in response to virus infection and include proteins from interferon-stimulated genes (ISGs). Many ISG proteins have been identified but relatively few have been characterized in detail and most studies have focused on studying their antiviral activities against particular viruses, such as influenza A viruses and human immunodeficiency virus (HIV)-1. This review summarizes current literature regarding host cell restriction factors against paramyxo- and pneumoviruses, on which there is more limited data. Alongside discussion of known restriction factors, this review also considers viral countermeasures in overcoming host restriction, the strengths and limitations in different experimental approaches in studies reported to date, and the challenges in reconciling differences between in vitro and in vivo data. Furthermore, this review provides an outlook regarding the landscape of emerging technologies and tools available to study host cell restriction factors, as well as the suitability of these proteins as targets for broad-spectrum antiviral therapeutics.
Topics: Animals; Biomarkers; Gene Expression Regulation, Viral; Host Specificity; Host-Pathogen Interactions; Humans; Immunity, Innate; Paramyxoviridae Infections; Paramyxovirinae; Pneumovirus; Pneumovirus Infections; Viral Tropism; Virus Replication
PubMed: 33276587
DOI: 10.3390/v12121381 -
Viruses May 2022Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe disease in humans and livestock. Due to its high pathogenicity in humans and the lack of...
Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe disease in humans and livestock. Due to its high pathogenicity in humans and the lack of available vaccines and therapeutics, NiV needs to be handled in biosafety level 4 (BSL-4) laboratories. Safe inactivation of samples containing NiV is thus necessary to allow further processing in lower containment areas. To date, there is only limited information available on NiV inactivation methods validated by BSL-4 facilities that can be used as a reference. Here, we compare some of the most common inactivation methods in order to evaluate their efficacy at inactivating NiV in infected cells, supernatants and organs. Thus, several physical and chemical inactivation methods, and combinations thereof, were assessed. Viral replication was monitored for 3 weeks and NiV presence was assessed by RT-qPCR, plaque assay and indirect immunofluorescence. A total of nineteen methods were shown to reduce NiV infectious particles in cells, supernatants and organs to undetectable levels. Therefore, we provide a list of methods for the safe and efficient inactivation of NiV.
Topics: Henipavirus Infections; Humans; Nipah Virus; Virus Replication
PubMed: 35632791
DOI: 10.3390/v14051052 -
The Lancet. Microbe Dec 2023
Topics: Humans; Henipavirus; Henipavirus Infections; Nervous System Physiological Phenomena
PubMed: 37804851
DOI: 10.1016/S2666-5247(23)00295-1 -
Journal of Virology Sep 2021We have developed a flexible platform for delivery of proteins to target cell interiors using paramyxovirus-like particles. The key enabling feature is an appendage, 15...
We have developed a flexible platform for delivery of proteins to target cell interiors using paramyxovirus-like particles. The key enabling feature is an appendage, 15 to 30 amino acid residues in length, that is added to cargo proteins and that induces them to bind to the viral matrix (M) protein during virus-like particle (VLP) assembly. The cargo is then incorporated within the VLPs as they bud, using the same interactions that normally direct viral genome packaging. The appendage can also serve as an epitope tag for cargo detection using a nucleocapsid (NP) protein-specific monoclonal antibody. Using this approach, we generated luciferase-loaded VLPs, green fluorescent protein-loaded VLPs, superoxide dismutase-loaded VLPs, and Cre recombinase-loaded VLPs. In each case, the VLPs could efficiently deliver their functional cargos to target cells and, in the case of Cre recombinase, to target cell nuclei. The strategy was employed using two different VLP production platforms, one based on parainfluenza virus 5 (PIV5) and the other based on Nipah virus, and in both cases efficient cargo packaging and delivery could be achieved. These findings provide a foundation for development of paramyxovirus-like particles as tools for safe and efficient delivery of therapeutic proteins to cells and tissues. Therapeutic proteins including transcription factors and genome editors have enormous clinical potential but are currently limited in part due to the challenges of safely and efficiently delivering these proteins to the interiors of target cells. Here, we have developed a new strategy for protein delivery based on manipulation of paramyxovirus genome packaging interactions.
Topics: Drug Delivery Systems; Genetic Engineering; Humans; Luciferases, Renilla; Nucleocapsid; Paramyxoviridae; Viral Matrix Proteins; Virion; Virus Assembly
PubMed: 34379508
DOI: 10.1128/JVI.01030-21 -
Viruses Dec 2021Pneumoviruses include pathogenic human and animal viruses, the most known and studied being the human respiratory syncytial virus (hRSV) and the metapneumovirus (hMPV),... (Review)
Review
Pneumoviruses include pathogenic human and animal viruses, the most known and studied being the human respiratory syncytial virus (hRSV) and the metapneumovirus (hMPV), which are the major cause of severe acute respiratory tract illness in young children worldwide, and main pathogens infecting elderly and immune-compromised people. The transcription and replication of these viruses take place in specific cytoplasmic inclusions called inclusion bodies (IBs). These activities depend on viral polymerase L, associated with its cofactor phosphoprotein P, for the recognition of the viral RNA genome encapsidated by the nucleoprotein N, forming the nucleocapsid (NC). The polymerase activities rely on diverse transient protein-protein interactions orchestrated by P playing the hub role. Among these interactions, P interacts with the NC to recruit L to the genome. The P protein also plays the role of chaperone to maintain the neosynthesized N monomeric and RNA-free (called N) before specific encapsidation of the viral genome and antigenome. This review aims at giving an overview of recent structural information obtained for hRSV and hMPV P, N, and more specifically for P-NC and N-P complexes that pave the way for the rational design of new antivirals against those viruses.
Topics: Animals; Antiviral Agents; Drug Design; Humans; Metapneumovirus; Models, Molecular; Nucleocapsid Proteins; Paramyxoviridae Infections; Phosphoproteins; Protein Binding; Protein Conformation; RNA, Viral; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Transcription, Genetic; Viral Proteins; Virus Replication
PubMed: 34960719
DOI: 10.3390/v13122449 -
Viruses Dec 2023Henipaviruses are zoonotic viruses, including some highly pathogenic and capable of serious disease and high fatality rates in both animals and humans. Hendra virus and... (Review)
Review
Henipaviruses are zoonotic viruses, including some highly pathogenic and capable of serious disease and high fatality rates in both animals and humans. Hendra virus and Nipah virus are the most notable henipaviruses, resulting in significant outbreaks across South Asia, South-East Asia, and Australia. Pteropid fruit bats have been identified as key zoonotic reservoirs; however, the increased discovery of henipaviruses outside the geographic distribution of Pteropid fruit bats and the detection of novel henipa-like viruses in other species such as the shrew, rat, and opossum suggest that Pteropid bats are not the sole reservoir for henipaviruses. In this review, we provide an update on henipavirus spillover events and describe the recent detection of novel unclassified henipaviruses, with a strong focus on the shrew and its emerging role as a key host of henipaviruses.
Topics: Humans; Animals; Rats; Henipavirus Infections; Shrews; Chiroptera; Nipah Virus; Hendra Virus
PubMed: 38140648
DOI: 10.3390/v15122407