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Virulence Dec 2023Recent viral hemorrhagic fever (VHF) disease outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV) in West Africa are unique and alarming. The intents of this...
Recent viral hemorrhagic fever (VHF) disease outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV) in West Africa are unique and alarming. The intents of this editorial are to highlight what is known about these viruses and the disease outbreaks that they cause in the African continent and elsewhere and to raise awareness of a related virus called Lassa virus (LASV) that causes endemic viral hemorrhagic fever infections and frequent outbreaks in West Africa.
Topics: Humans; Hemorrhagic Fevers, Viral; Lassa virus; Ebolavirus; Africa, Western; Disease Outbreaks; Hemorrhagic Fever, Ebola
PubMed: 36748841
DOI: 10.1080/21505594.2023.2176980 -
Virulence Dec 2023A new virus, named Langya henipavirus (LayV), has recently been identified in Shandong and Henan provinces in China and has so far infected 35 individuals between April...
A new virus, named Langya henipavirus (LayV), has recently been identified in Shandong and Henan provinces in China and has so far infected 35 individuals between April 2018 and August 2021. It is closely related to other known henipaviruses (Nipah and Hendra viruses) that can cause up to 70% human case fatality. Even though LayV has not been shown to be fatal in humans and does not appear to be transmitted from human-to-human, it is an RNA virus with the capacity to evolve genetically in the infected hosts (e.g. shrews) and can infect humans (e.g. farmers who have been in close contacts with shrews). It is therefore important to be vigilant about this new viral outbreak.
Topics: Humans; Animals; Public Health; Shrews; Henipavirus Infections; Nipah Virus
PubMed: 36599832
DOI: 10.1080/21505594.2022.2154188 -
Antiviral mechanisms of two broad-spectrum monoclonal antibodies for rabies prophylaxis and therapy.Frontiers in Immunology 2023Rabies is an acute and lethal encephalomyelitis caused by lyssaviruses, among which rabies virus (RABV) is the most prevalent and important for public health. Although...
Rabies is an acute and lethal encephalomyelitis caused by lyssaviruses, among which rabies virus (RABV) is the most prevalent and important for public health. Although preventable through the post-exposure administration of rabies vaccine and immunoglobulins (RIGs), the disease is almost invariably fatal since the onset of clinical signs. Two human neutralizing monoclonal antibodies (mAbs), RVC20 and RVC58, have been shown to be effective in treating symptomatic rabies. To better understand how these mAbs work, we conducted structural modeling and assays to analyze their mechanisms of action, including their ability to mediate Fc-dependent effector functions. Our results indicate that both RVC20 and RVC58 recognize and lock the RABV-G protein in its pre-fusion conformation. RVC58 was shown to neutralize more potently the extra-cellular virus, while RVC20 mainly acts by reducing viral spreading from infected cells. Importantly, RVC20 was more effective in promoting effector functions compared to RVC58 and 17C7-RAB1 mAbs, the latter of which is approved for human rabies post-exposure treatment. These results provide valuable insights into the multiple mechanisms of action of RVC20 and RVC58 mAbs, offering relevant information for the development of these mAbs as treatment for human rabies.
Topics: Humans; Antiviral Agents; Rabies; Rabies Vaccines; Rabies virus; Antibodies, Monoclonal; Broadly Neutralizing Antibodies
PubMed: 37638057
DOI: 10.3389/fimmu.2023.1186063 -
ELife Nov 2023Transsynaptic viral vectors provide means to gain genetic access to neurons based on synaptic connectivity and are essential tools for the dissection of neural circuit...
Transsynaptic viral vectors provide means to gain genetic access to neurons based on synaptic connectivity and are essential tools for the dissection of neural circuit function. Among them, the retrograde monosynaptic ΔG-Rabies has been widely used in neuroscience research. A recently developed engineered version of the ΔG-Rabies, the non-toxic self-inactivating (SiR) virus, allows the long term genetic manipulation of neural circuits. However, the high mutational rate of the rabies virus poses a risk that mutations targeting the key genetic regulatory element in the SiR genome could emerge and revert it to a canonical ΔG-Rabies. Such revertant mutations have recently been identified in a SiR batch. To address the origin, incidence and relevance of these mutations, we investigated the genomic stability of SiR in vitro and in vivo. We found that "revertant" mutations are rare and accumulate only when SiR is extensively amplified in vitro, particularly in suboptimal production cell lines that have insufficient levels of TEV protease activity. Moreover, we confirmed that SiR-CRE, unlike canonical ΔG-Rab-CRE or revertant-SiR-CRE, is non-toxic and that revertant mutations do not emerge in vivo during long-term experiments.
Topics: Humans; Rabies; Rabies virus; Mutation; Cell Line; Genomic Instability
PubMed: 37921437
DOI: 10.7554/eLife.83459 -
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 -
Microbiology Spectrum Aug 2023Respiratory viruses may interfere with each other and affect the epidemic trend of the virus. However, the understanding of the interactions between respiratory viruses...
Respiratory viruses may interfere with each other and affect the epidemic trend of the virus. However, the understanding of the interactions between respiratory viruses at the population level is still very limited. We here conducted a prospective laboratory-based etiological study by enrolling 14,426 patients suffered from acute respiratory infection (ARI) in Beijing, China during 2005 to 2015. All 18 respiratory viruses were simultaneously tested for each nasal and throat swabs collected from enrolled patients using molecular tests. The virus correlations were quantitatively evaluated, and the respiratory viruses could be divided into two panels according to the positive and negative correlations. One included influenza viruses (IFVs) A, B, and respiratory syncytial virus (RSV), while the other included human parainfluenza viruses (HPIVs) 1/3, 2/4, adenovirus (Adv), human metapneumovirus (hMPV), and enterovirus (including rhinovirus, named picoRNA), α and β human coronaviruses (HCoVs). The viruses were positive-correlated in each panel, while negative-correlated between panels. After adjusting the confounding factors by vector autoregressive model, positive interaction between IFV-A and RSV and negative interaction between IFV-A and picoRNA are still be observed. The asynchronous interference of IFV-A significantly delayed the peak of β human coronaviruses epidemic. The binary property of the respiratory virus interactions provides new insights into the viral epidemic dynamics in human population, facilitating the development of infectious disease control and prevention strategies. Systematic quantitative assessment of the interactions between different respiratory viruses is pivotal for the prevention of infectious diseases and the development of vaccine strategies. Our data showed stable interactions among respiratory viruses at human population level, which are season irrelevant. Respiratory viruses could be divided into two panels according to their positive and negative correlations. One included influenza virus and respiratory syncytial virus, while the other included other common respiratory viruses. It showed negative correlations between the two panels. The asynchronous interference between influenza virus and β human coronaviruses significantly delayed the peak of β human coronaviruses epidemic. The binary property of the viruses indicated transient immunity induced by one kind of virus would play role on subsequent infection, which provides important data for the development of epidemic surveillance strategies.
Topics: Humans; Infant; Prospective Studies; Viruses; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Orthomyxoviridae
PubMed: 37378522
DOI: 10.1128/spectrum.00019-23 -
Journal of Virology Oct 2023Ebola disease (EBOD) is a public health threat with a high case fatality rate. Most EBOD outbreaks have occurred in remote locations, but the 2013-2016 Western Africa...
Ebola disease (EBOD) is a public health threat with a high case fatality rate. Most EBOD outbreaks have occurred in remote locations, but the 2013-2016 Western Africa outbreak demonstrated how devastating EBOD can be when it reaches an urban population. Here, the 2022 Sudan virus disease (SVD) outbreak in Mubende District, Uganda, is summarized, and the genetic relatedness of the new variant is evaluated. The Mubende variant exhibited 96% amino acid similarity with historic SUDV sequences from the 1970s and a high degree of conservation throughout the outbreak, which was important for ongoing diagnostics and highly promising for future therapy development. Genetic differences between viruses identified during the Mubende SVD outbreak were linked with epidemiological data to better interpret viral spread and contact tracing chains. This methodology should be used to better integrate discrete epidemiological and sequence data for future viral outbreaks.
Topics: Humans; Disease Outbreaks; Ebolavirus; Hemorrhagic Fever, Ebola; Uganda; Genetic Variation; Contact Tracing
PubMed: 37750724
DOI: 10.1128/jvi.00590-23 -
Open Veterinary Journal Sep 2023Nipah Virus (NiV) is a highly virulent pathogen that poses a significant threat to human and animal populations. This review provides a comprehensive overview of the... (Review)
Review
Nipah Virus (NiV) is a highly virulent pathogen that poses a significant threat to human and animal populations. This review provides a comprehensive overview of the latest control and prevention strategies against NiV, focusing on vaccine development, antiviral drug discovery, early diagnosis, surveillance, and high-level biosecurity measures. Advancements in vaccine research, including live-attenuated vaccines, virus-like particles, and mRNA-based vaccines, hold promise for preventing NiV infections. In addition, antiviral drugs, such as remdesivir, ribavirin, and favipiravir, have the potential to inhibit NiV replication. Early diagnosis through molecular and serological assays, immunohistochemistry, and real-time reverse transcription polymerase chain reaction plays a crucial role in timely detection. Surveillance efforts encompassing cluster-based and case-based systems enhance outbreak identification and provide valuable insights into transmission dynamics. Furthermore, the implementation of high-level biosecurity measures in agriculture, livestock practices, and healthcare settings is essential to minimize transmission risks. Collaboration among researchers, public health agencies, and policymakers is pivotal in refining and implementing these strategies to effectively control and prevent NiV outbreaks and safeguard public health on a global scale.
Topics: Humans; Animals; Nipah Virus; Disease Outbreaks; Henipavirus Infections
PubMed: 37842102
DOI: 10.5455/OVJ.2023.v13.i9.1 -
Clinical and Experimental Immunology Dec 2023Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of... (Review)
Review
Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of protection. Increasing evidence suggests that Fc-mediated antibody effector functions have an important role, but little is known about the development, heterogeneity, and durability of these functional responses. In light of future vaccine strategies, a clear view of the immunological background and differences between various target populations is of crucial importance. In this study, we have assessed both quantitative and qualitative aspects of RSV-specific serum antibodies, including IgG/IgA levels, IgG subclasses, antibody-dependent complement deposition, cellular phagocytosis, and NK cell activation (ADNKA). Samples were collected cross-sectionally in different age groups (11-, 24-, and 46-month-old children, adults, and older adults; n = 31-35 per group) and longitudinally following natural RSV infection in (older) adults (2-36 months post-infection; n = 10). We found that serum of 24-month-old children induces significantly lower ADNKA than the serum of adults (P < 0.01), which is not explained by antibody levels. Furthermore, in (older) adults we observed boosting of antibody levels and functionality at 2-3 months after RSV infection, except for ADNKA. The strongest decrease was subsequently observed within the first 9 months, after which levels remained relatively stable up to three years post-infection. Together, these data provide a comprehensive overview of the functional landscape of RSV-specific serum antibodies in the human population, highlighting that while antibodies reach adult levels already at a young age, ADNKA requires more time to fully develop.
Topics: Infant; Child; Humans; Aged; Child, Preschool; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Antibodies, Viral; Immunoglobulin G; Antibodies, Neutralizing
PubMed: 37605554
DOI: 10.1093/cei/uxad101 -
Pediatric Annals Mar 2024
Topics: Humans; Immunization; Vaccination; Respiratory Syncytial Virus, Human
PubMed: 38466331
DOI: 10.3928/19382359-20240214-01