Nipah and Hendra Viruses: Deadly Zoonotic Paramyxoviruses with the Potential to Cause the Next Pandemic

Thakur V., Thakur P., Ratho R.K.

Geisbert T.W., Bobb K., Borisevich V., Geisbert J.B., Agans K.N., Cross R.W., Prasad A.N., Fenton K.A., Yu H., Fouts T.R., Broder C.C., Dimitrov A.S.

Nipah and Hendra viruses are highly pathogenic bat-borne paramyxoviruses recently included in the WHO Blueprint priority diseases list. A fully registered horse anti-Hendra virus subunit vaccine has been in use in Australia since 2012. Based on the same immunogen, the Hendra virus attachment glycoprotein ectodomain, a subunit vaccine formulation for use in people is now in a Phase I clinical trial. We report that a single dose vaccination regimen of this human vaccine formulation protects against otherwise lethal challenges of either Hendra or Nipah virus in a nonhuman primate model. The protection against the Nipah Bangladesh strain begins as soon as 7 days post immunization with low dose of 0.1 mg protein subunit. Our data suggest this human vaccine could be utilized as efficient emergency vaccine to disrupt potential spreading of Nipah disease in an outbreak setting.

Epstein J.H., Anthony S.J., Islam A., Kilpatrick A.M., Ali Khan S., Balkey M.D., Ross N., Smith I., Zambrana-Torrelio C., Tao Y., Islam A., Quan P.L., Olival K.J., Khan M.S., Gurley E.S., et. al.

Significance Nipah virus (NiV) is a zoonotic virus and World Health Organization (WHO) priority pathogen that causes near-annual outbreaks in Bangladesh and India with >75% mortality. This work advances our understanding of transmission of NiV in its natural bat reservoir by analyzing data from a 6-y multidisciplinary study of serology, viral phylogenetics, bat ecology, and immunology. We show that outbreaks in Pteropus bats are driven by increased population density, loss of immunity over time, and viral recrudescence, resulting in multiyear interepizootic periods. Incidence is low, but bats carry NiV across Bangladesh and can shed virus at any time of year, highlighting the importance of routes of transmission to the timing and location of human NiV outbreaks.

Amaya M., Broder C.C.

Hendra virus (HeV) and Nipah virus (NiV) are bat-borne zoonotic para-myxoviruses identified in the mid- to late 1990s in outbreaks of severe disease in livestock and people in Australia and Malaysia, respectively. HeV repeatedly re-emerges in Australia while NiV continues to cause outbreaks in South Asia (Bangladesh and India), and these viruses have remained transboundary threats. In people and several mammalian species, HeV and NiV infections present as a severe systemic and often fatal neurologic and/or respiratory disease. NiV stands out as a potential pandemic threat because of its associated high case-fatality rates and capacity for human-to-human transmission. The development of effective vaccines, suitable for people and livestock, against HeV and NiV has been a research focus. Here, we review the progress made in NiV and HeV vaccine development, with an emphasis on those approaches that have been tested in established animal challenge models of NiV and HeV infection and disease.

Playford E.G., Munro T., Mahler S.M., Elliott S., Gerometta M., Hoger K.L., Jones M.L., Griffin P., Lynch K.D., Carroll H., El Saadi D., Gilmour M.E., Hughes B., Hughes K., Huang E., et. al.

The monoclonal antibody m102.4 is a potent, fully human antibody that neutralises Hendra and Nipah viruses in vitro and in vivo. We aimed to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of m102.4 in healthy adults.In this double-blind, placebo-controlled, single-centre, dose-escalation, phase 1 trial of m102.4, we randomly assigned healthy adults aged 18-50 years with a body-mass index of 18·0-35·0 kg/m2 to one of five cohorts. A sentinel pair for each cohort was randomly assigned to either m102.4 or placebo. The remaining participants in each cohort were randomly assigned (5:1) to receive m102.4 or placebo. Cohorts 1-4 received a single intravenous infusion of m102.4 at doses of 1 mg/kg (cohort 1), 3 mg/kg (cohort 2), 10 mg/kg (cohort 3), and 20 mg/kg (cohort 4), and were monitored for 113 days. Cohort 5 received two infusions of 20 mg/kg 72 h apart and were monitored for 123 days. The primary outcomes were safety and tolerability. Secondary outcomes were pharmacokinetics and immunogenicity. Analyses were completed according to protocol. The study was registered on the Australian New Zealand Clinical Trials Registry, ACTRN12615000395538.Between March 27, 2015, and June 16, 2016, 40 (52%) of 77 healthy screened adults were enrolled in the study. Eight participants were assigned to each cohort (six received m102.4 and two received placebo). 86 treatment-emergent adverse events were reported, with similar rates between placebo and treatment groups. The most common treatment-related event was headache (12 [40%] of 30 participants in the combined m102.4 group, and three [30%] of ten participants in the pooled placebo group). No deaths or severe adverse events leading to study discontinuation occurred. Pharmacokinetics based on those receiving m102.4 (n=30) were linear, with a median half-life of 663·3 h (range 474·3-735·1) for cohort 1, 466·3 h (382·8-522·3) for cohort 2, 397·0 h (333·9-491·8) for cohort 3, and 466·7 h (351·0-889·6) for cohort 4. The elimination kinetics of those receiving repeated dosing (cohort 5) were similar to those of single-dose recipients (median elimination half-time 472·0 [385·6-592·0]). Anti-m102.4 antibodies were not detected at any time-point during the study.Single and repeated dosing of m102.4 were well tolerated and safe, displayed linear pharmacokinetics, and showed no evidence of an immunogenic response. This study will inform future dosing regimens for m102.4 to achieve prolonged exposure for systemic efficacy to prevent and treat henipavirus infections.Queensland Department of Health, the National Health and Medical Research Council, and the National Hendra Virus Research Program.

Shuai L., Ge J., Wen Z., Wang J., Wang X., Bu Z.

Nipah virus (NiV) is a re-emerging zoonotic pathogen that causes high mortality in humans and pigs. Oral immunization in free-roaming animals is one of the most practical approaches to prevent NiV pandemics. We previously generated a recombinant rabies viruses (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain, rERAG333E, which contains a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G333E) and serves as an oral vaccine for dog rabies. In this study, we generated two recombinant RABVs, rERAG333E/NiVG and rERAG333E/NiVF, expressing the NiV Malaysian strain attachment glycoprotein (NiV-G) or fusion glycoprotein (NiV-F) gene based on the rERAG333E vector platform. Both rERAG333E/NiVG and rERAG333E/NiVF displayed growth properties similar to those of rERAG333E and caused marked syncytia formation after co-infection in BSR cell culture. Adult and suckling mice intracerebrally inoculated with the recombinant RABVs showed NiV-G and NiV-F expression did not increase the virulence of rERAG333E. Oral vaccination with rERAG333E/NiVG either singularly or combined with rERAG333E/NiVF induced significant NiV neutralizing antibody against NiV and RABV, and IgG to NiV-G or NiV-F in mice and pigs. rERAG333E/NiVG and rERAG333E/NiVF thus appeared to be suitable candidates for further oral vaccines for potential animal targets in endemic areas of NiV disease and rabies.

Dang H.V., Chan Y., Park Y., Snijder J., Da Silva S.C., Vu B., Yan L., Feng Y., Rockx B., Geisbert T.W., Mire C.E., Broder C.C., Veesler D.

Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50–100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals. An antibody that recognizes the F glycoproteins from Nipah and Hendra viruses can neutralize both viruses and recognizes a quaternary epitope in the prefusion F trimer, preventing conformational changes required for fusion.

van Doremalen N., Lambe T., Sebastian S., Bushmaker T., Fischer R., Feldmann F., Haddock E., Letko M., Avanzato V.A., Rissanen I., LaCasse R., Scott D., Bowden T.A., Gilbert S., Munster V.

Nipah virus (NiV) is a highly pathogenic re-emerging virus that causes outbreaks in South East Asia. Currently, no approved and licensed vaccine or antivirals exist. Here, we investigated the efficacy of ChAdOx1 NiVB, a simian adenovirus-based vaccine encoding NiV glycoprotein (G) Bangladesh, in Syrian hamsters. Prime-only as well as prime-boost vaccination resulted in uniform protection against a lethal challenge with NiV Bangladesh: all animals survived challenge and we were unable to find infectious virus either in oral swabs, lung or brain tissue. Furthermore, no pathological lung damage was observed. A single-dose of ChAdOx1 NiVB also prevented disease and lethality from heterologous challenge with NiV Malaysia. While we were unable to detect infectious virus in swabs or tissue of animals challenged with the heterologous strain, a very limited amount of viral RNA could be found in lung tissue by in situ hybridization. A single dose of ChAdOx1 NiVB also provided partial protection against Hendra virus and passive transfer of antibodies elicited by ChAdOx1 NiVB vaccination partially protected Syrian hamsters against NiV Bangladesh. From these data, we conclude that ChAdOx1 NiVB is a suitable candidate for further NiV vaccine pre-clinical development.

Aditi, Shariff M.

AbstractNipah virus (NiV) is an emerging bat-borne pathogen. It was first identified 20 years ago in Malaysia and has since caused outbreaks in other parts of South and Southeast Asia. It causes severe neurological and respiratory disease which is highly lethal. It is highly infectious and spreads in the community through infected animals or other infected people. Different strains of the virus show differing clinical and epidemiological features. Rapid diagnosis and implementation of infection control measures are essential to contain outbreaks. A number of serological and molecular diagnostic techniques have been developed for diagnosis and surveillance. Difficulties in diagnosis and management arise when a new area is affected. The high mortality associated with infection and the possibility of spread to new areas has underscored the need for effective management and control. However, no effective treatment or prophylaxis is readily available, though several approaches show promise. Given the common chains of transmission from bats to humans, a One Health approach is necessary for the prevention and control of NiV infection.

Hassan M.Z., Sazzad H.M., Luby S.P., Sturm-Ramirez K., Bhuiyan M.U., Rahman M.Z., Islam M.M., Ströher U., Sultana S., Kafi M.A., Daszak P., Rahman M., Gurley E.S.

Nipah virus (NiV) has been transmitted from patient to caregivers in Bangladesh presumably through oral secretions. We aimed to detect whether NiV-infected patients contaminate hospital surfaces with the virus. During December 2013-April 2014, we collected 1 swab sample from 5 surfaces near NiV-infected patients and tested surface and oral swab samples by real-time reverse transcription PCR for NiV RNA. We identified 16 Nipah patients; 12 cases were laboratory-confirmed and 4 probable. Of the 12 laboratory-confirmed cases, 10 showed NiV RNA in oral swab specimens. We obtained surface swab samples for 6 Nipah patients; 5 had evidence of NiV RNA on >1 surface: 4 patients contaminated towels, 3 bed sheets, and 1 the bed rail. Patients with NiV RNA in oral swab samples were significantly more likely than other Nipah patients to die. To reduce the risk for fomite transmission of NiV, infection control should target hospital surfaces.

Ewer K., Sebastian S., Spencer A.J., Gilbert S., Hill A.V., Lambe T.

The 2014-15 Ebola outbreak in West Africa highlighted the potential for large disease outbreaks caused by emerging pathogens and has generated considerable focus on preparedness for future epidemics. Here we discuss drivers, strategies and practical considerations for developing vaccines against outbreak pathogens. Chimpanzee adenoviral (ChAd) vectors have been developed as vaccine candidates for multiple infectious diseases and prostate cancer. ChAd vectors are safe and induce antigen-specific cellular and humoral immunity in all age groups, as well as circumventing the problem of pre-existing immunity encountered with human Ad vectors. For these reasons, such viral vectors provide an attractive platform for stockpiling vaccines for emergency deployment in response to a threatened outbreak of an emerging pathogen. Work is already underway to develop vaccines against a number of other outbreak pathogens and we will also review progress on these approaches here, particularly for Lassa fever, Nipah and MERS.

Walpita P., Cong Y., Jahrling P.B., Rojas O., Postnikova E., Yu S., Johns L., Holbrook M.R.

Nipah virus is a highly lethal zoonotic paramyxovirus that was first recognized in Malaysia during an outbreak in 1998. During this outbreak, Nipah virus infection caused a severe febrile neurological disease in humans who worked in close contact with infected pigs. The case fatality rate in humans was approximately 40%. Since 2001, NiV has re-emerged in Bangladesh and India where fruit bats (Pteropus spp.) have been identified as the principal reservoir of the virus. Transmission to humans is considered to be bat-to-human via food contaminated with bat saliva, or consumption of contaminated raw date palm sap, although human-to-human transmission of Nipah virus has also been documented. To date, there are no approved prophylactic options or treatment for NiV infection. In this study, we produced mammalian cell-derived native Nipah virus-like particles composed of Nipah virus G, F and M proteins for use as a novel Nipah virus vaccine. Previous studies demonstrated that the virus-like particles were structurally similar to authentic virus, functionally assembled and immunoreactive. In the studies reported here, purified Nipah virus-like particles were utilized either alone or with adjuvant to vaccinate golden Syrian hamsters with either three-dose or one-dose vaccination regimens followed by virus challenge. These studies found that Nipah virus-like particle immunization of hamsters induced significant neutralizing antibody titers and provided complete protection to all vaccinated animals following either single or three-dose vaccine schedules. These studies prove the feasibility of a virus-like particle-based vaccine for protection against Nipah virus infection. A vaccine candidate consisting of virus-like particles could offer the first effective prophylaxis against the deadly Nipah virus. Endemic to Malaysia, Bangladesh, and India, Nipah virus is contracted from infected fruit bats and causes severe inflammation of the brain. Pramila Walpita, of the University of Hawaii, working with colleagues at the United States’ National Institute of Allergy and Infectious Diseases, developed an effective vaccine of immunity-generating Nipah virus surface proteins without the virus’ disease-causing genetic material. Their vaccine elicited a significant protective antibody response, with 100% of vaccinated animals surviving subsequent Nipah virus infection. Despite its prevalence and lethality, Nipah virus has no licensed vaccine and poses a serious problem to the developing countries it affects. Walpita’s vaccine candidate could offer a much-needed treatment option and warrants further investigation and pre-clinical trials.

Gurley E.S., Hegde S.T., Hossain K., Sazzad H.M., Hossain M.J., Rahman M., Sharker M.A., Salje H., Islam M.S., Epstein J.H., Khan S.U., Kilpatrick A.M., Daszak P., Luby S.P.

Preventing emergence of new zoonotic viruses depends on understanding determinants for human risk. Nipah virus (NiV) is a lethal zoonotic pathogen that has spilled over from bats into human populations, with limited person-to-person transmission. We examined ecologic and human behavioral drivers of geographic variation for risk of NiV infection in Bangladesh. We visited 60 villages during 2011-2013 where cases of infection with NiV were identified and 147 control villages. We compared case villages with control villages for most likely drivers for risk of infection, including number of bats, persons, and date palm sap trees, and human date palm sap consumption behavior. Case villages were similar to control villages in many ways, including number of bats, persons, and date palm sap trees, but had a higher proportion of households in which someone drank sap. Reducing human consumption of sap could reduce virus transmission and risk for emergence of a more highly transmissible NiV strain.

Rissanen I., Ahmed A.A., Azarm K., Beaty S., Hong P., Nambulli S., Duprex W.P., Lee B., Bowden T.A.

In 2012, cases of lethal pneumonia among Chinese miners prompted the isolation of a rat-borne henipavirus (HNV), Mòjiāng virus (MojV). Although MojV is genetically related to highly pathogenic bat-borne henipaviruses, the absence of a conserved ephrin receptor-binding motif in the MojV attachment glycoprotein (MojV-G) indicates a differing host-cell recognition mechanism. Here we find that MojV-G displays a six-bladed β-propeller fold bearing limited similarity to known paramyxoviral attachment glycoproteins, in particular at host receptor-binding surfaces. We confirm the inability of MojV-G to interact with known paramyxoviral receptors in vitro, indicating an independence from well-characterized ephrinB2/B3, sialic acid and CD150-mediated entry pathways. Furthermore, we find that MojV-G is antigenically distinct, indicating that MojV would less likely be detected in existing large-scale serological screening studies focused on well-established HNVs. Altogether, these data indicate a unique host-cell entry pathway for this emerging and potentially pathogenic HNV. The attachment glycoprotein (HNV-G) of henipaviruses interacts with host receptors at the cell surface and is a major determinant of species tropism. Here the authors provide structural and functional evidence that the emergent henipavirus, Mòjiang virus, uses an entry mechanism that is independent of known paramyoxviral cellular receptors.

Tiong V., Lam C., Phoon W., AbuBakar S., Chang L.

The genes for Nipah virus (NiV) proteins were amplified from viral RNA, cloned into the plasmid pTriEx-3 Hygro, expressed, and purified using immobilized metal affinity chromatography. The recombinant N, F, and G NiV proteins (rNiV-N, rNiV-F, and rNiV-G), were successfully expressed in Escherichia coli and purified with a yield of 4, 16, and 4 mg/L, respectively. All 3 recombinant viral proteins reacted with all 19 samples of NiV-positive human sera. The rNiV-N and rNiV-G proteins were the most immunogenic. The recombinant viral proteins did not react with any of the 12 NiV-negative sera. However, serum from a patient with a late-onset relapsing NiV infection complication was found to be primarily reactive to rNiV-G only. Additionally, there is a distinctive variation in the profile of antigen-reactive bands between the sample from a case of relapsing NiV encephalitis and that of acute NiV infection. The overall findings of this study suggest that the recombinant viral proteins have the potential to be developed further for use in the detection of NiV infection, and continuous biosurveillance of NiV infection in resource-limited settings.

Gondelaud F., Bignon C., Ptchelkine D., Carrière F., Longhi S.

AbstractThe Hendra (HeV) and Nipah (NiV) viruses are high‐priority, biosafety level‐4 pathogens that cause fatal neurological and respiratory disease. Their P gene encodes not only the P protein, an essential polymerase cofactor, but also the virulence factors V and W. We previously showed that the W protein of HeV (WHeV) forms amyloid‐like fibrils and that one of its subdomains, PNT3, fibrillates in isolation. However, the fibrillation kinetics is much faster in the case of the full‐length WHeV compared to PNT3, suggesting that another WHeV region contributes to the fibrillation process. In this work, we identified the region spanning residues 2–110 (PNT1) as the crucial region implicated in WHeV fibrillation. Through site‐directed mutagenesis, combined with thioflavin T binding experiments and negative‐staining transmission electron microscopy, we showed that a predicted cryptic amyloidogenic region (CAR) within PNT1 is the main driver of fibrillation and deciphered the underlying molecular mechanism. Using FTIR, we showed that PNT1 fibrils are enriched in cross β‐sheets. Sequence alignment revealed conservation of the CAR across the Henipavirus genus and enabled the identification of a hitherto never reported pro‐amyloidogenic motif. The ability to form fibrils was experimentally shown to be a common property shared by Henipavirus PNT1 proteins. Overall, this study sheds light on the molecular mechanisms underlying WHeV fibrillation and calls for future studies aimed at exploring the relevance of the newly identified pro‐amyloidogenic motif as a valuable target for antiviral approaches.

Ruedas-Torres I., Findlay-Wilson S., Kennedy E., Dowall S., Salguero F.J.

Nipah virus (NiV) is recognized as one of the key pathogens with pandemic potential. We have recently established a NiV hamster model, which reproduces a highly similar disease to that observed in human cases, including respiratory and neurological signs and lesions. The aims of this study were to describe the microscopic lesions observed in the golden Syrian hamster model after intranasal (IN) and intraperitoneal (IP) inoculation with different doses of the Malaysian strain of NiV; to describe in depth the cell composition of the pulmonary and the brain lesions and the expression of proinflammatory cytokines in-situ using a combination of histopathological techniques including immunohistochemistry (IHC) and in-situ hybridisation (ISH) via RNAscope technique. We also developed a multiplex IHC which will allow us to study the interaction of the virus with cell populations in the lung and brain in future studies. For this, we selected 28 lung and brain formalin-fixed paraffin-embedded (FFPE) samples from previous experiments performed by our research group. Histopathology revealed severe pulmonary broncho-interstitial pneumonia, mainly in animals inoculated via the IN route, accompanied by a strong acute inflammatory response (Iba1+ cells) and high levels of NiV RNA. Upregulation of proinflammatory cytokines (IL-6 and TNF) was also observed by ISH RNAscope technique in these animals. Neurological lesions, consisting of perivascular cuffing and meningitis, were observed mainly in animals inoculated via IP route. IHC results showed astrocytosis (GFAP+) and microgliosis (Iba1+) in the brain of these animals, together with mild levels of IL6 and TNF mRNA. These results have helped us to characterize the host-pathogen interaction in the golden Syrian hamster animal model of NiV infection that is being currently used in preclinical testing of antiviral and vaccine strategies. Techniques used in this study could be applied to the development and application of golden Syrian hamster models of other infections by henipaviruses, including Hendra virus (HeV), and other high consequence priority pathogens.

Kane Y., Nalikka B., Tendu A., Omondi V., Bienes K.M., Padane A., Duong V., Berthet N., Wong G.

Nayak S.

Abstract Langya henipavirus (LayV) and Mojiang henipavirus (MojV) are emerging zoonotic pathogens that were first identified in China in 2018 and 2012 respectively, and are classified within the Henipavirus genus. This article presents an in-depth review of LayV and MojV, focusing on their structural properties, viral entrance, and consequences for human health. The pathogenic potential of these viruses is investigated in depth as well as the current diagnostic methods for identifying LayV and MojV. Furthermore, treatment methods for controlling LayV and MojV infections are assessed, with a particular emphasis on the critical need for tailored antiviral research. This review serves as a critical resource for researchers and healthcare professionals, offering an up-to-date synthesis of knowledge on LayV and MojV while underscoring their significance in public health.

Li J., Liu Y., He R., Huang Z., Huang W., Huang H., Liu Z., Chen G.

Yang Y., Wang Y., Campbell D.E., Lee H., Beatty W., Wang L., Baldridge M., López C.B.

Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized eGFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection. As expected, SLC35A1 knockout (KO) cells showed drastic reduction in infections with SeV, NDV and MuV due to the lack of cell surface sialic acids receptors. However, SLC35A2 KO cells revealed unknown critical roles for this factor in virus-cell and cell-to-cell fusion events for the different paramyxoviruses. While UGT was essential for virus-cell fusion during SeV entry to the cell, it was not required for NDV or MuV entry. Importantly, UGT promoted the formation of syncytia during MuV infection, suggesting a role in cell-to-cell virus spread. Our findings demonstrate that paramyxoviruses can bind to or enter A549 cells in the absence of canonical galactose-bound sialic-acid decorations and show that UGT facilitates paramyxovirus fusion processes involved in entry and spread.

Branda F., Ceccarelli G., Giovanetti M., Albanese M., Binetti E., Ciccozzi M., Scarpa F.

The re-emergence of the Nipah virus (NiV) in Kerala, India, following the tragic death of a 14-year-old boy, underscores the persistent threat posed by zoonotic pathogens and highlights the growing global public health challenge. With no vaccine or curative treatment available, and fatality rates as high as 94% in past outbreaks, the Nipah virus is a critical concern for health authorities worldwide. Transmitted primarily through contact with fruit bats or consumption of contaminated food, as well as direct human-to-human transmission, NiV remains a highly lethal and unpredictable pathogen. The World Health Organization has classified Nipah as a priority pathogen due to its alarming potential to cause widespread outbreaks and even trigger the next pandemic. Recent outbreaks in India and Bangladesh, occurring with seasonal regularity, have once again exposed the vulnerability of public health systems in containing this virus. This study explores the epidemiology, ecological factors driving transmission, and the public health response to NiV, emphasizing the role of zoonotic spillovers in pandemic preparedness. As the global community grapples with an increasing number of emerging infectious diseases, the Nipah virus stands as a stark reminder of the importance of coordinated surveillance, rapid containment measures, and the urgent development of novel strategies to mitigate the impact of this re-emerging threat.

Mohan G., Choudhury A., Bhat J., Phartyal R., Lal R., Verma M.

The urgency to understand the complex interactions between viruses, their animal reservoirs, and human populations has been necessitated by the continuous spread of zoonotic viral diseases as evidenced in epidemics and pandemics throughout human history. Riboviruses are involved in some of the most prevalent human diseases, responsible for causing epidemics and pandemics. These viruses have an animal origin and have been known to cross the inter-species barrier time and time again, eventually infecting human beings. Their evolution has been a long road to harbour important adaptations for increasing fitness, mutability and virulence; a result of natural selection and mutation pressure, making these viruses highly infectious and difficult to counter. Accumulating favourable mutations in the course, they imitate the GC content and codon usage patterns of the host for maximising the chances of infection. A myriad of viral and host factors determine the fate of specific viral infections, which may include virus protein and host receptor compatibility, host restriction factors and others. Thus, understanding the biology, transmission and molecular mechanisms of Riboviruses is essential for the development of effective antiviral treatments, vaccine development and strategies to prevent and control viral infections. Keeping these aspects in mind, this review aims to provide a holistic approach towards understanding Riboviruses.

Popov I.V., Donnik I.M., Lipilkina T.A., Berezinskaia I.S., Tkacheva E.V., Lukbanova E.A., Aleshukina A.V., Tikhmeneva I.A., Derezina T.N., Evsyukov A.P., Tverdokhlebova T.I., Ermakov A.M.

Bats (Chiroptera) are the second most diverse order of mammals after rodents, which ensures their key role in the functioning of ecosystems. The microbiota of bats, especially the bacterial one, is poorly studied, which does not allow an accurate assessment of the role of bats in global microbial ecology. In this study, we determined the composition and diversity of the intestinal microbiota of the common noctule (Nyctalus noctula) in Rostov-on-Don using bacteriological analysis and metagenomic sequencing of the V3-V4 16S rRNA gene. As a result, we found that microbial diversity determined using metagenomic sequencing was statistically significantly higher (p 0.001) compared to the bacteriological method. However, mass spectrometric identification of bacterial isolates made it possible to determine their species, while the sensitivity of the metagenomic sequencing protocol used is limited to reliable identification of bacteria to genus rank. Also, bacteria of the genera Enterococcus, Citrobacter, Enterobacter, Lactococcus, and Latilactobacillus were the most prevalent in the intestinal microbiota of the common noctule. Our study provides the first data on the composition of the cultivated and uncultivated microbiota of the rufous noctule, which is a fundamental step in the study of the microbiota of synanthropic bats.

Jin D., Zhang L., Peng C., He M., Wang W., Li Z., Liu C., Du J., Zhou J., Yin L., Shan C., Qin Y., Chen M.

Wu X., Xiang R., Yang D., He X., Zhu L., Sun F., Li H., Pi N., Li Y.

Roth J.A., Galyon J.

Food insecurity is a serious and immediate concern for the world due to challenges including overpopulation; conflicts; animal, plant, and human diseases; climate change; depletion of resources; and environmental degradation. Long-term solutions for food production must consider the impacts on the environment, water and other resources, human and animal health, and sustainable crop production. The fundamental cause of food insecurity is the rapid and unprecedented increase in human population from approximately 2 billion people in 1925 to over 8 billion in 2023. The need for food has led to major expansion of both crop and food animal production including movement into new areas; increased production requires more resources, some of which are being depleted. This paper focuses on food animal production. Humans depend on three major species for most animal-origin food: Chickens (meat and eggs), cattle (meat and milk), and swine (meat). Each species is currently threatened by diseases that can rapidly spread internationally, and some have zoonotic potential. Diversification of animal-based food, such as expanding aquaculture can help to protect against food shortages should an epizootic occur in one or more of the above species. Cutting-edge science is needed to improve food animal production and pathogen control. This requires an interdisciplinary one-world, one-health approach led by international organizations and funded by the developed world. An optimal response will involve scientists and policy experts from government, the private sector, and universities worldwide. Strengthening all nations' public health infrastructure and veterinary services is essential to this aim. Fortunately, concerns about worldwide food security are concurrent with rapid advances in nearly all aspects of science, which can be applied to sustainably increase food production both locally and globally. There must be a collective will to apply science and to implement policies to solve current food security problems and to prepare for future challenges.

Popov I.V., Donnik I.M., Lipilkina T.A., Berezinskaia I.S., Tkacheva E.V., Lukbanova E.A., Aleshukina A.V., Tikhmeneva I.A., Derezina T.N., Evsyukov A.P., Tverdokhlebova T.I., Ermakov A.M.

Since bats are the second most diverse order of mammals after rodents, they play a key role in the functioning of ecosystems. The microbiota of bats, especially the bacterial one, is poorly studied, which hinders accurate assessment of the role of bats in microbial ecology. In this study, we determined the composition and diversity of the intestinal microbiota of the common noctule (Nyctalus noctula) in Rostov-on-Don using bacteriological analysis and metagenomic sequencing of the 16S rRNA gene V3–V4 region. Microbial diversity determined using metagenomic sequencing was found to be statistically significantly higher (p < 0.001) compared to that determined by the bacteriological method. However, mass spectral identification of bacterial isolates at the species level was possible, while the sensitivity of the metagenomic sequencing protocol used was limited to reliable identification at the genus level. Bacteria of the genera Enterococcus, Citrobacter, Enterobacter, Lactococcus, and Latilactobacillus were predominant in the intestinal microbiota of the common noctule. Our study provides the first data on the composition of the cultured and uncultured microbiota of the common noctule, which is a fundamental step in the study of the microbiota of synanthropic bats.

Mohapatra P., Nazli Khatib M., Shabil M., Rajput P., Sharma N., Satapathy P., Bhopte K., Jena D., Sah S., Bushi G.

Branda F., Pavia G., Ciccozzi A., Quirino A., Marascio N., Matera G., Romano C., Locci C., Azzena I., Pascale N., Sanna D., Casu M., Ceccarelli G., Ciccozzi M., Scarpa F.

The family Paramyxoviridae includes a number of negative RNA viruses known for their wide host range and significant zoonotic potential. In recent years, there has been a surge in the identification of emerging zoonotic paramyxoviruses, particularly those hosted by bat species, which serve as key reservoirs. Among these, the genera Henipavirus and Pararubulavirus are of particular concern. Henipaviruses, including the highly pathogenic Hendra and Nipah viruses, have caused severe outbreaks with high mortality rates in both humans and animals. In contrast, zoonotic pararubulaviruses such as the Menangle virus typically induce mild symptoms or remain asymptomatic in human hosts. This review summarizes current knowledge on the evolution, ecology, and epidemiology of emerging zoonotic paramyxoviruses, focusing on recently discovered viruses and their potential to cause future epidemics. We explore the molecular mechanisms underlying host-switching events, viral replication strategies, and immune evasion tactics that facilitate interspecies transmission. In addition, we discuss ecological factors influencing virus emergence, including changes in bat populations and habitats and the role of wildlife–human interfaces. We also examine the public health impact of these emerging viruses, underlining the importance of enhanced surveillance, developing improved diagnostic tools, and implementing proactive strategies to prevent potential outbreaks. By providing a comprehensive overview of recent advances and gaps in knowledge, this review aims to inform future research directions and public health policies related to zoonotic paramyxoviruses.