Human Encephalitis Research Articles

First parechovirus reported case in Saudi Arabia in hospitalized immunocompromised adult patient

Human parechovirus, a member of the Picornaviridae family (PeVs), can lead to severe infections, including severe meningitis, meningoencephalitis, and sepsis-like syndrome. We report a case of human parechovirus-related encephalitis in a 52-year-old woman diagnosed with glioblastoma multiforme. She underwent surgical resection in June 2022. Unfortunately, her disease recurred, and she underwent a second resection in August 2022, followed by radiation therapy and Temozolomide therapy. She presented to the hospital with acute confusion followed by seizures, necessitating intubation for airway support. A cerebrospinal fluid (CSF) sample was obtained and processed using the Biofire FilmArray, which reported the detection of HSV-1. Despite being on Acyclovir, the patient did not show signs of improvement. Consequently, a second CSF sample was obtained and sent for next-generation sequencing (NGS), which returned a positive result for Parechovirus. In this presented case, the patient exhibited symptoms of an unknown infectious cause. The utilization of NGS and metagenomic analysis helped identify Parechovirus as the primary pathogen present, in addition to previously identified HSV. This comprehensive approach facilitated a thorough assessment of the underlying infection and guided targeted treatment. In conclusion, the application of NGS techniques and metagenomic analysis proved instrumental in identifying the root cause of the infection.

Comparative study of virus and lymphocyte distribution with clinical data suggests early high dose immunosuppression as potential key factor for the therapy of patients with BoDV-1 infection

ABSTRACT Borna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies. ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1act: general activation of microglial cells; Iba1nod: formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; patearly: patients treated with early high dose steroid shot; patlate: patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum

Japanese encephalitis virus NS1 and NS1' proteins induce vimentin rearrangement via the CDK1-PLK1 axis to promote viral replication.

Japanese encephalitis virus (JEV) is a mosquito-borne orthoflavivirus that causes severe encephalitis in humans, particularly in Asia. Despite the availability of a safe and effective vaccine, JEV infection remains a significant public health threat due to limited vaccination coverage. Understanding the interactions between JEV and host proteins is essential for developing more effective antiviral strategies. In this study, we investigated the role of vimentin, an intermediate filament protein, in JEV replication. Our findings reveal that JEV NS1 and NS1' proteins induce vimentin rearrangement, resulting in the formation of cage-like structures that envelop the viral replication factories (RFs), thus facilitating efficient viral replication. Our research highlights the importance of the interplay between the cytoskeleton and orthoflavivirus, suggesting that targeting vimentin could be a promising approach for the development of antiviral strategies to inhibit JEV propagation.

Biophysical and structural study of La Crosse virus endonuclease inhibition for the development of new antiviral options.

The large Bunyavirales order includes several families of viruses with a segmented ambisense (-) RNA genome and a cytoplasmic life cycle that starts by synthesizing viral mRNA. The initiation of transcription, which is common to all members, relies on an endonuclease activity that is responsible for cap-snatching. In La Crosse virus, an orthobunyavirus, it has previously been shown that the cap-snatching endonuclease resides in the N-terminal domain of the L protein. Orthobunyaviruses are transmitted by arthropods and cause diseases in cattle. However, California encephalitis virus, La Crosse virus and Jamestown Canyon virus are North American species that can cause encephalitis in humans. No vaccines or antiviral drugs are available. In this study, three known Influenza virus endonuclease inhibitors (DPBA, L-742,001 and baloxavir) were repurposed on the La Crosse virus endonuclease. Their inhibition was evaluated by fluorescence resonance energy transfer and their mode of binding was then assessed by differential scanning fluorimetry and microscale thermophoresis. Finally, two crystallographic structures were obtained in complex with L-742,001 and baloxavir, providing access to the structural determinants of inhibition and offering key information for the further development of Bunyavirales endonuclease inhibitors.

Human Parechovirus-induced Encephalitis: Clinical and Neuroimaging Outcomes in Infants Under Three Months of Age (P7-13.010)

Human Parechovirus-induced Encephalitis: Clinical and Neuroimaging Outcomes in Infants Under Three Months of Age (P7-13.010)

Spatiotemporal heterogeneity and potential drivers of human tick-borne encephalitis in the south of Russian Far East

The south of the Russian Far East is distinguished by diversity of natural conditions for the presence of vectors and circulation of pathogens, primarily tick-borne infections. Despite the relatively low proportion of tick-borne encephalitis in the structure of tick-borne infections and the rather low incidence rate compared to other Russian regions, the disease here has epidemiological significance, which is associated with its severe course. Therefore, it is important to identify local areas of greatest epidemic manifestation of the disease and potential drivers influencing the spread of tick-borne encephalitis. This study uses data on population incidence in the municipal districts of Khabarovsk Krai, Amur Oblast, Jewish Autonomous Oblast and Zabaikalsky Krai between 2000 and 2020. Based on Kulldorf spatial scanning statistics, a temporally stable cluster of virus circulation in the population in the southwest of Zabaikalsky Krai was identified, which existed during 2009-2018. Regression modeling using zero-inflated negative binomial regression based on a set of environmental and socio-economic predictors allowed to identify variables determining the probability of infection: the share of forest, the amount of precipitation in the warm period, population density, as well as variables reflecting population employment and socio-economic well-being. Despite the fact that tick-borne encephalitis is a natural focal disease and may be characterized by natural periods of increased incidence, the influence of the social component can have a strong impact on the epidemiological manifestation. The identified spatio-temporal differences within the study region and potential drivers must be taken into account when developing a set of preventive measures.

Seroepidemiological survey to cell culture rabies vaccines (CCRV) in Brazil

Rabies is a contagious viral disease that can be easily transmitted by the saliva and brain/nervous system tissues of the infected animals, causing severe and fatal encephalitis in both animals and humans. Vaccination campaigns are crucial to combat and prevent rabies's spread in dogs and humans. The Modified Fuenzalida & Palicios vaccines have been widely used since the 70s and have proven effective in producing a solid serological response. Since 2008, the Brazilian Ministry of Health has introduced a Cell Culture Rabies Vaccine (CCRV) for all dog mass vaccination campaigns in Brazil. However, to date, there is limited evidence on the immunologic response of dogs to this type of vaccine in field conditions. The present study evaluated the serological response in dogs vaccinated with CCRV from blood samples of 724 dogs using the Simplified Fluorescence Inhibition Microtest – SFIMT. Dogs with a titer equal to 0.5 IU/mL or above were considered seropositive. The results revealed that 59.12% (428/724) of all dogs tested and 48.49% (32/66) of primo-vaccinated animals were seropositive. The percentage of seronegative animals was higher than seropositive for animals that received a single dose during their life (p < 0.05). The opposite was observed in animals with five or more doses. The results of this study demonstrated that the CCRV vaccines elicit a satisfactory immunological response in field conditions and can constitute an essential population-level preventive strategy as part of annual canine rabies vaccination campaigns. Although its effectiveness has been studied, there is limited evidence of its immunological response in dogs under field conditions. This paper evaluates the serological response to CCRV in dogs vaccinated during mass vaccination campaigns from 2012 to 2017.

Impact of Toll-Like Receptors (TLRs) and TLR Signaling Proteins in Trigeminal Ganglia Impairing Herpes Simplex Virus 1 (HSV-1) Progression to Encephalitis: Insights from Mouse Models.

Herpes simplex virus 1 (HSV-1) or simplexvirus humanalpha 1 is a neurotropic virus that is responsible for orofacial infections in humans. More than 70% of the world's population may have seropositivity for HSV-1, and this virus is a leading cause of sporadic lethal encephalitis in humans. The role of toll-like receptors (TLRs) in defending against HSV-1 infection has been explored, including the consequences of lacking these receptors or other proteins in the TLR pathway. Cell and mouse models have been used to study the importance of these receptors in combating HSV-1, how they relate to the innate immune response, and how they participate in the orchestration of the adaptive immune response. Myeloid differentiation factor 88 (MyD88) is a protein involved in the downstream activation of TLRs and plays a crucial role in this signaling. Mice with functional MyD88 or TLR2 and TLR9 can survive HSV-1 infection. However, they can develop encephalitis and face a 100% mortality rate in a dose-dependent manner when MyD88 or TLR2 plus TLR9 proteins are non-functional. In TLR2/9 knockout mice, an increase in chemokines and decreases in nitric oxide (NO), interferon (IFN) gamma, and interleukin 1 (IL-1) levels in the trigeminal ganglia (TG) have been correlated with mortality.

Factors Involved in the Immunological Protection against Rabies Virus in Dogs in Spain.

Rabies, a viral disease spread by infected animal bites that causes encephalitis in humans and other mammals, is a neglected infectious disease present on all continents except Antarctica. Spain has been free of terrestrial rabies since 1978. However, due to its geographical situation, it represents a bridge for imported cases from an endemic continent such as Africa to Europe. Rabies vaccination in dogs is an essential preventive tool against this zoonosis. The aim of this study was to determine the state of the immune response against rabies virus in dogs in Spain and to demonstrate whether several factors that have been previously related to the influence of the seroprevalence of this species are involved here. The seroconversion level of this zoonotic virus was assessed in a total of 1060 animals. Indirect ELISA was used to obtain data for statistical analysis to evaluate the studied variables. Working under the concept of One Health, this study provides relevant information to be taken into consideration not only to prevent re-emergence in countries free of this disease but also for prevention and control in endemic countries.

Engagement of AKT and ERK signaling pathways facilitates infection of human neuronal cells with West Nile virus

West Nile virus (WNV) is an important neurotropic virus that accounts for the emergence of human arboviral encephalitis and meningitis. The interaction of WNV with signaling pathways plays a key role in controlling WNV infection. We have investigated the roles of the AKT and ERK pathways in supporting WNV propagation and modulating the inflammatory response following WNV infection. WNV established a productive infection in neuronal cell lines originated from human and mouse. Expression of IL-11 and TNF-α was markedly up-regulated in the infected human neuronal cells, indicating elicitation of inflammation response upon WNV infection. WNV incubation rapidly activated signaling cascades of AKT (AKT-S6-4E-BP1) and ERK (MEK-ERK-p90RSK) pathways. Treatment with AKT inhibitor MK-2206 or MEK inhibitor U0126 abrogated WNV-induced AKT or ERK activation. Strong activation of AKT and ERK signaling pathways could be detectable at 24 h after WNV infection, while such activation was abolished at 48 h post infection. U0126 treatment or knockdown of ERK expression significantly increased WNV RNA levels and viral titers and efficiently decreased IL-11 production induced by WNV, suggesting the involvement of ERK pathway in WNV propagation and IL-11 induction. MK-2206 treatment enhanced WNV RNA replication accompanied with a moderate decrease in IL-11 production. These results demonstrate that engagement of AKT and ERK signaling pathways facilitates viral infection and may be implicated in WNV pathogenesis.

One Health in action: Investigation of the first detected local cluster of fatal borna disease virus 1 (BoDV-1) encephalitis, Germany 2022

BackgroundZoonotic Borna disease virus 1 (BoDV-1) causes fatal encephalitis in humans and animals. Subsequent to the detection of two paediatric cases in a Bavarian municipality in Germany within three years, we conducted an interdisciplinary One Health investigation. We aimed to explore seroprevalence in a local human population with a risk for BoDV-1 exposure as well as viral presence in environmental samples from local sites and BoDV-1 prevalence within the local small mammal population and its natural reservoir, the bicoloured white-toothed shrew (Crocidura leucodon). MethodsThe municipality's adult residents participated in an anonymised sero-epidemiological study. Potential risk factors and clinical symptoms were assessed by an electronic questionnaire. Small mammals, environmental samples and ticks from the municipality were tested for BoDV-1-RNA. Shrew-derived BoDV-1-sequences together with sequences of the two human cases were phylogenetically analysed. ResultsIn total, 679 citizens participated (response: 41 %), of whom 38 % reported shrews in their living environment and 19 % direct shrew contact. No anti-BoDV-1 antibodies were detected in human samples. BoDV-1-RNA was also undetectable in 38 environmental samples and 336 ticks. Of 220 collected shrews, twelve of 40 C. leucodon (30%) tested BoDV-1-RNA-positive. BoDV-1-sequences from the previously diagnosed two paediatric patients belonged to two different subclades, that were also present in shrews from the municipality. InterpretationOur data support the interpretation that human BoDV-1 infections are rare even in endemic areas and primarily manifest as severe encephalitis. Sequence analysis linked both previous paediatric human infections to the local shrew population, but indicated independent infection sources. FundingThe project was partly financed by funds of the German Federal Ministry of Education and Research (grant numbers: 01KI2005A, 01KI2005C, 01KI1722A, 01KI1722C, 01KI2002 to MaBe, DR, RGU, DT, BS) as well as by the ReForM-A programme of the University Hospital Regensburg (to MaBa) and by funds of the Bavarian State Ministry of Health, Care and Prevention, project “Zoonotic Bornavirus Focal Point Bavaria – ZooBoFo” (to MaBa, MaBe, BS, MMB, DR, PS, RGU).

Natural products and derivatives as Japanese encephalitis virus antivirals.

Japanese encephalitis virus (JEV) causes acute Japanese encephalitis (JE) in humans and reproductive disorders in pigs. There are ~68 000 cases of JE worldwide each year, with ~13 600-20 400 deaths. JE infections have a fatality rate of one-third, and half of the survivors experience permanent neurological sequelae. The disease is prevalent throughout the Asia-Pacific region and has the potential to spread globally. JEV poses a serious threat to human life and health, and vaccination is currently the only strategy for long-term sustainable protection against JEV infection. However, licensed JEV vaccines are not effective against all strains of JEV. To date, there are no drugs approved for clinical use, and the development of anti-JEV drugs is urgently needed. Natural products are characterized by a wide range of sources, unique structures, and low prices, and this paper provides an overview of the research and development of anti-JEV bioactive natural products.

Development of Colloidal Gold-Based Immunochromatographic Strips for Rapid Detection and Surveillance of Japanese Encephalitis Virus in Dogs across Shanghai, China.

Japanese encephalitis virus (JEV) causes acute encephalitis in humans and is of major public health concern in most Asian regions. Dogs are suitable sentinels for assessing the risk of JEV infection in humans. A neutralization test (NT) or an enzyme-linked immunosorbent assay (ELISA) is used for the serological detection of JEV in dogs; however, these tests have several limitations, and, thus, a more convenient and reliable alternative test is needed. In this study, a colloidal gold immunochromatographic strip (ICS), using a purified recombinant EDIII protein, was established for the serological survey of JEV infection in dogs. The results show that the ICSs could specifically detect JEV antibodies within 10 min without cross-reactions with antibodies against other canine viruses. The test strips could detect anti-JEV in serum with dilution up to 640 times, showing high sensitivity. The coincidence rate with the NT test was higher than 96.6%. Among 586 serum samples from dogs in Shanghai examined using the ICS test, 179 (29.98%) were found to be positive for JEV antibodies, and the high seropositivity of JEV in dogs in China was significantly correlated with the season and living environment. In summary, we developed an accurate and economical ICS for the rapid detection of anti-JEV in dog serum samples with great potential for the surveillance of JEV in dogs.

Cellular nuclear-localized U2AF2 protein is hijacked by the flavivirus 3’UTR for viral replication complex formation and RNA synthesis

Japanese encephalitis virus (JEV) is a zoonotic pathogen belonging to the Flavivirus genus, causing viral encephalitis in humans and reproductive failure in swine. The 3’ untranslated region (3’UTR) of JEV contains highly conservative secondary structures required for viral translation, RNA synthesis, and pathogenicity. Identification of host factors interacting with JEV 3’UTR is crucial for elucidating the underlying mechanism of flavivirus replication and pathogenesis. In this study, U2 snRNP auxiliary factor 2 (U2AF2) was identified as a novel cellular protein that interacts with the JEV genomic 3’UTR (the SL-I, SL-II, SL-III, and DB region) via its 1 to 148 amino acids. JEV infection or JEV 3’ UTR on its own triggered the nuclear-localized U2AF2 redistributed to the cytoplasm and colocalized with viral replication complex. U2AF2 also interacts with JEV NS3 and NS5 protein, the downregulation of U2AF2 nearly abolished the formation of flavivirus replication vesicles. The production of JEV protein, RNA, and viral titers were all increased by U2AF2 overexpression and decreased by knockdown. U2AF2 also functioned as a pro-viral factor for Zika virus (ZIKV) and West Nile virus (WNV), but not for vesicular stomatitis virus (VSV). Mechanically, U2AF2 facilitated the synthesis of both positive- and negative-strand flavivirus RNA without affecting viral attachment, internalization or release process. Collectively, our work paves the way for developing U2AF2 as a potential flavivirus therapeutic target.

Infectivity and Potential Zoonotic Characteristics of Porcine Pseudorabies Virus in Human Cells

Pseudorabies virus (PRV) is widely spread, characterized by high contagiousness, high viral load, and strong infectivity, and poses severe threats to the global pig farming industry. Apart from pigs, PRV can also infect several other mammals, including mice, cattle, cats, dogs, and wolves, with diverse clinical symptoms. Notably, approximately more than 20 cases of human PRV infection have been reported in recent years, with fever, seizures, human encephalitis, intraocular inflammation, and severe central nervous system symptoms. However, whether PRV can infect humans or belongs to a zoonotic virus is still controversial. In this study, human neuronal cells were infected with PRV and blindly passaged to obtain human cell‐adapted PRV, followed by comparing the characteristics of human cell‐adapted PRV and pig‐derived PRV in vitro and in vivo, to determine whether PRV has the potential to infect humans. The results showed that PRV could be stably passaged in human cells and produced progeny viruses similar to the parental virus, including morphology, infectivity, and pathogenicity. The human cell‐adapted PRV can also cross‐transmit to cells from other origins, including humans, mice, pigs, and monkeys, causing different cytopathic effects. Moreover, multiple tissue damage can be detected in mice infected with human cell‐adapted PRV. These results demonstrate that PRV is a potential zoonotic virus, and it is necessary to pay close attention to the spread and variation of the virus in animals and humans.

Chapter 23 - Infectious leukoencephalopathies

Leukoencephalopathy from infectious agents may have a rapid course, such as human simplex virus encephalitis; however, in many diseases, it may take months or years before diagnosis, such as in subacute sclerosing panencephalitis or Whipple disease. There are wide geographic distributions and susceptible populations, including both immunocompetent and immunodeficient patients. Many infections have high mortality rates, such as John Cunningham virus and subacute sclerosing panencephalitis, although others have effective treatments if suspected and treated early, such as herpes simplex encephalitis. This chapter will describe viral, bacterial, and protozoal infections, which predominantly cause leukoencephalopathy. We focus on the clinical presentation of these infectious agents briefly covering epidemiology and subtypes of infections. Next, we detail current pathophysiologic mechanisms causing white matter injury. Diagnostic and confirmatory tests are discussed. We cover predominantly MRI imaging features of leukoencephalopathies, and in addition, summarize the common imaging features. Additionally, we detail how imaging features may be used to narrow the differential of a leukoencephalopathy clinical presentation. Lastly, we present an outline of common treatment approaches where available.

Characteristics of Madariaga and Venezuelan Equine Encephalitis Virus Infections, Panama.

Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, clinical and epidemiologic reports are limited, and outbreaks are occurring at an increasing frequency. We addressed the data gap by analyzing all available clinical and epidemiologic data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 human alphavirus encephalitis cases were detected in Panama during 1961‒2023. We described the clinical signs and symptoms and epidemiologic characteristics of those cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection compared with those of other arbovirus infections occurring in the region. Our results highlight the challenges for the clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.

Serological Investigation of Japanese Encephalitis Virus Infection in Commercially Reared Pigs, Southwestern Nigeria.

Japanese encephalitis virus (JEV) is a zoonotic arbovirus that causes abortion, stillbirth, and congenital defects in pigs, and epidemic encephalitis in humans. Currently, there is scarcity of information on JEV infection in pigs in Nigeria. Since the Culex tritaeniorhynchus vector of JEV is present in Nigeria and considering recent anecdotal reports of abortions and birth of weak piglets in some pig farms in southwestern Nigeria, there is a need for studies on the presence of the virus and its true burden among pig populations in the country. Serum samples (n=368) obtained from farm-reared pigs in four States of southwestern Nigeria were screened for JEV-specific IgG antibodies using a commercial ELISA kit. An overall JEV seropositivity of 35.1% (95% CI: 30.18 - 39.93%) was obtained, with detectable antibodies in pigs of all age groups, breeds, sex, and locations. Our results suggest natural exposure of these unvaccinated intensively reared pigs to JEV circulating silently in the swine population with significant association of the seropositivity with location (state/community in which the pig farms exist) and breed of the pigs studied. This first report of detection of anti-JEV antibodies in pigs in Nigeria indicates that JEV circulated among these pigs and underscores the need for active surveillance for JEV in humans, pigs, and mosquitoes to provide valuable epidemiological data for the design of effective control strategies against the virus, thus forestalling potential future outbreaks of the infection.

Emergence of genotype III St. Louis encephalitis virus in the western United States potentially linked to a wetland in Argentina

St. Louis encephalitis virus (SLEV) is endemic in the Americas and its transmission networks involve Culex mosquitoes and avian species. In 2015, a human encephalitis outbreak took place in Arizona and California, indicating the re-emergence of this pathogen in the US. Viral strains isolated in that outbreak belong to genotype III SLEV previously detected only in South America. In this study, genotype III SLEV was detected in mosquitoes collected in Mar Chiquita Lagoon (Córdoba, Argentina), an overwintering site for numerous migratory bird species. The genotype III SLEV sequence detected in this site shares the closest known ancestor with those introduced in Arizona in 2015. Our results highlight the potential significance of wetlands as key sites for arbovirus maintenance and emergence.

Inactivated Recombinant Rabies Virus Displaying the Nipah Virus Envelope Glycoproteins Induces Systemic Immune Responses in Mice.

Nipah virus (NiV) causes severe, lethal encephalitis in humans and pigs. However, there is no licensed vaccine available to prevent NiV infection. In this study, we used the reverse genetic system based on the attenuated rabies virus strain SRV9 to construct two recombinant viruses, rSRV9-NiV-F and rSRV9-NiV-G, which displayed the NiV envelope glycoproteins F and G, respectively. Following three immunizations in BALB/c mice, the inactivated rSRV9-NiV-F and rSRV9-NiV-G alone or in combination, mixed with the adjuvants ISA 201 VG and poly (I:C), were able to induce the antigen-specific cellular and Th1-biased humoral immune responses. The specific antibodies against rSRV9-NiV-F and rSRV9-NiV-G had reactivity with two constructed bacterial-like particles displaying the F and G antigens of NiV. These data demonstrate that rSRV9-NiV-F or rSRV9-NiV-G has the potential to be developed into a promising vaccine candidate against NiV infection.