Three decades of #discovery: An overview of #Hendra virus, the original #Henipavirus

 

Abstract

Hendra virus (HeV) emerged in Australia in 1994, causing a devastating outbreak among horses in Brisbane with spread to humans, resulting in one death. This nonsegmented, negative-stranded RNA virus belongs to the family Paramyxoviridae and represents the first zoonotic paramyxovirus isolated from bats. Flying foxes (genus Pteropus) serve as the natural reservoir, with all four mainland Australian species carrying antibodies with no apparent disease. HeV initiates infection by binding ephrin-B2 receptors on vascular endothelial cells, driving characteristic pathology involving vasculitis, thrombosis, and neurological complications. Horses are amplifying hosts, shedding virus abundantly in respiratory secretions and posing transmission risks to humans during invasive procedures. To date, seven confirmed human infections have been documented, with a 57% fatality rate, presenting as severe respiratory disease or progressive encephalitis. Two genetic variants are now recognized: the original HeV genotype 1 and the emerging HeV genotype 2, identified in limited equine cases. Recent surveillance of bat roosts revealed substantial viral diversity, with peak shedding occurring during winter—coinciding with equine spillover peaks. Prevention integrates multiple strategies: the licensed equine vaccine Equivac which provides One Health protection for both horses and human contacts; biosecurity measures including proper PPE; and habitat restoration to reduce nutritional stress in bat populations. Emerging therapeutics include monoclonal antibodies, with m102.4 showing cross-protective activity against both HeV and the closely related Nipah virus. No licensed human vaccines currently exist, though candidates are in development. Future prevention strategies increasingly recognize the importance of Indigenous-led conservation approaches alongside biomedical interventions. This review will focus on the history of HeV, virus replication and diversity, epidemiology, clinical manifestations, diagnosis, treatment, prevention, as well as ecological and interdisciplinary countermeasures.

Author summary

Hendra virus (HeV) was first detected in 1994, with two outbreaks occurring within 2 months of that year. One was the index outbreak in the Brisbane suburb of Hendra, and the other was retrospectively diagnosed in the following year. This review examines the discoveries that have been made in the 30 years since its discovery.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014138

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The temporal #sequence of #influenza #H1N1 and #Mycoplasma pneumoniae co-infection causes disease severity in Syrian hamster models

 

Abstract

Introduction: 

Influenza H1N1 virus is one of the most prevalent subtypes among influenza viruses, and co-infection with Mycoplasma pneumoniae (Mp) is frequently documented in clinical respiratory infections. However, the pathological mechanisms underlying the temporal sequence of H1N1-Mp co-infection remain poorly characterized, and relevant animal models are lacking.

Methods: 

In this study, we established a model of influenza H1N1 and Mycoplasma pneumoniae co-infection in Syrian hamsters and infected two pathogens in interval of 72 hours. Clinical manifestations, body temperature, body weight, pathogen loads in nasal, pharyngeal, and anal swabs, as well as blood cytokine profiles were dynamically monitored over 14 days post-infection (dpi). Additionally, tissue pathogen loads, histopathological changes, routine blood parameters, and blood biochemistry indicators were evaluated at 7 and 14 dpi.

Results: 

The results demonstrated that hamsters first infected with H1N1 followed by Mp (F-M group) exhibited significantly more severe histopathological lesions (assessed by HE staining), higher pathogen loads, and dysregulated cytokine responses compared to other infection groups.

Conclusion: 

Our findings highlight the critical role of infection order in determining the severity of H1N1-Mp co-infection, providing novel insights into the temporal dynamics and pathogenic mechanisms of respiratory co-infections.

Source: 

Link: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2026.1787294/full

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#Pathogenesis of #H5N1 Clade 2.3.4.4b in dry Jersey #cows following intramammary inoculation shows within-host compartmentalization

 

Abstract

Dairy cattle have emerged as a prolific amplifying host for highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b and a new source for cross-species and zoonotic transmission. Independent introductions of H5N1 with unclear exposure routes have been reported in several dairy herds across the U.S. These events escalate the pandemic potential of HPAIV H5N1 as transmission within and between mammalian species present opportunities for mammalian adapted H5N1 viruses to emerge. Although more than 1000 herds have been infected, bovine H5N1 influenza virus pathogenesis, transmission, and evolution in dairy cattle remains not well characterized. Working with H5N1-infected lactating cattle in high containment has been a major challenge due to the required infrastructure and logistics associated with housing, husbandry, and waste management for this model. Thus, developing alternative bovine models that maintain biological relevance while reducing operational complexity is warranted. Here, we evaluate the susceptibility of lactating Jersey cattle in the dry-off period, and characterize the effect of inoculation dose on the mammary pathogenicity of HPAIV H5N1 genotype B3.13. The results of this study demonstrate that dairy cows 21 days into the dry-off period are highly susceptible to HPAIV H5N1, recapitulating the severe clinical and pathological outcomes observed in infected lactating cows under experimental conditions and in field cases. We also observed an association between virus dose and the onset and severity of mastitis in individual udder-quarters and compartmentalized clonal expansion of variant populations. Overall, this study demonstrates that dry cows can provide a feasible model to study H5N1 virology, pathology, and humoral immunology in dairy cows.

Competing Interest Statement

The J.A.R. laboratory received support from Tonix Pharmaceuticals, Genus plc, Xing Technologies and Zoetis outside of the reported work. J.A.R. is inventor on patents and patent applications, owned by Kansas State University, on the use of antivirals and vaccines for the treatment and prevention of virus infections. The other authors declare no competing interests.

Funder Information Declared

This work was supported by the National Bio and Agro-Defense Facility (NBAF) Transition Fund from the State of Kansas, the USDA Animal Plant Health Inspection Service’s NBAF Scientist Training Program, the AMP and MCB Cores of the Center on Emerging and Zoonotic Infectious Diseases (CEZID) , and the NIAID supported Centers of Excellence for Influenza Research and Response (CEIRR, contract number 75N93021C00016 and subcontract A21-0702-S001). NIGMS. The sequencing infrastructure used in the study was funded by the USDA Animal Plant Health Inspection Services (AP20VSD&B000C086), while sequencing methodology development was funded in part by the USDA National Institute of Food and Agriculture (NIFA) Agriculture and Food Research Initiative (AFRI) (award no. 2021-68014-33635). H.M.M. was supported in part by NIAID T32055397.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.04.709389v1

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A lethal mouse #model of #Oz virus #infection reveals hepatic involvement and enables evaluation of #antiviral and #vaccine efficacy

 

Abstract

Oz virus (OZV), a member of the genus Thogotovirus in the family Orthomyxoviridae, is an emerging tick-borne virus reported in Japan. A fatal human case and seroepidemiological evidence of widespread exposure among wild animals and humans suggest its potential public health significance. However, no animal models suitable for pathogenic studies or evaluation of countermeasures are available for OZV. Here, we have established a lethal mouse model of OZV infection using cell-adapted virus and mice lacking type I interferon signaling (B6 Ifnar1 KO mice). OZV infection resulted in 100% mortality and was characterized by robust viral replication in the liver and spleen, severe hepatitis, and acute liver injury. Using this model, we also demonstrated that oral administration of T-705, an antiviral drug widely used against RNA viruses, as well as immunization with an inactivated whole virus particle vaccine, protected B6 Ifnar1 KO mice from lethal OZV infection by mitigating the acute hepatitis. The present study provides critical insights into OZV pathogenesis and establishes a practical in vivo platform for the development of countermeasures against OZV infection.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Japan Society for the Promotion of Science, 25K18810, 25K09431

Japan Agency for Medical Research and Development, JP223fa627005, JP24wm0225044

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.29.702403v1

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#Pathology of dose dependent inocula of #H5N8 avian #influenza viruses in experimentally infected #chicken

 

Abstract

In the present study, we assessed the pathogenicity of H5N8 avian influenza viruses belongs to the clade 2.3.4.4b in chicken. Birds of three different dose groups, 10 2 , 10 4 , and 10 6 EID 50 were used in the study. No mortality was observed in 10 2 EID0 group. Percent cumulative mortality of 10 4 and 10 6 EID 50 group was 66.67 and 100 %, respectively. Varying duration of MDT of 3.2 and 2 days was observed in 10 4 and 10 6 EID 50 group, respectively. The CID 50 of virus was found to be 10 4.5 EID 50 . High no. of viral RNA copies were found both in oropharyngeal and cloacal swabs and in various organs of birds infected in 10 4 and 10 6 EID 50 group. Significant gross and histological changes and presence of viral antigen in various organs were observed in 10 4 and 10 6 EID 50 group. So, the study concludes that Indian HPAI, H5N8 isolates are highly pathogenic in nature to chicken by affecting most organs systemically. CID 50 of this H5N8 virus indicates poor adaption in chicken and it implies poor transmission possibility of this virus for host species in field condition. Though this virus are highly pathogenic in nature as that of HPAI, H5N1 viruses, absence of endothelial staining in most organs attributes variation in replication process and pathogenesis from HPAI, H5N1 viruses. Hence, further studies need to be done to elucidate the pathobiology of this virus in various bird species.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Indian Council of Agricultural Research, https://ror.org/04fw54a43

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.27.700741v1

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#Infection and #transmission dynamics of #bovine and #human #influenza A #H5N1 viruses in mouse and hamster #models

 

Abstract

Here we investigated the pathogenesis and contact transmission of bovine- and human-derived highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b genotype B3.13 viruses in mammalian models. Using reverse genetics, we rescued three naturally occurring viruses: rTX2/24 (bovine-derived), rTexas/37 and rMichigan/90 (both human-derived), and compared their infection dynamics, replication and pathogenicity with the wild-type bovine TX2/24 strain in vitro and in vivo. All four viruses demonstrated comparable replication kinetics in four mammalian cell lines. However, the rMichigan/90 strain exhibited significantly smaller plaques in bovine and human cells. In vivo studies showed that mice infected with any of the viruses succumbed to infection within 4-5 days; however, mice infected with the rMichigan/90 virus exhibited slightly lower viral replication and shedding compared to the other strains. Similarly, as in the mouse experiments, in hamsters, all viruses induced body weight loss and oral shedding, with robust virus replication observed in tissues, but the rMichigan/90 virus presented reduced replication and shedding. Contact transmission studies in hamsters revealed limited transmissibility for these viruses, with only one out of four animals inoculated with the rMichigan/90 virus transmitting it to a naive contact. These findings indicate that both bovine- and human-derived H5N1 genotype B3.13 viruses present high pathogenicity in mammals, though the overall transmissibility remains low.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

College of Veterinary Medicine Research Office and the Office of the Vice Provost for Research, NIH/NIAID, 109022

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.17.700113v1

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#Pathobiology of Highly Pathogenic Avian #Influenza A #H5N1 Clade 2.3.4.4b Virus from #Pinnipeds on Tyuleniy Island in the Sea of #Okhotsk, #Russia

 

Abstract

Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b has recently emerged as a major threat to wildlife, agriculture, and public health due to its expanding host range and the increasing frequency of spillover into mammals. In July–August 2023, the mass death of over 3500 northern fur seals (Callorhinus ursinus) and at least one Steller sea lion (Eumetopias jubatus) was recorded on Tyuleniy Island in the Sea of Okhotsk, Russia. Two HPAI A(H5N1) viruses were isolated from fur seal carcasses and designated A/Northern_fur_seal/Russia_Tyuleniy/74/2023 and A/Northern_fur_seal/Russia_Tyuleniy/75/2023. Both viruses exhibited high pathogenicity in chickens (IVPI 2.7–3.0) and mice (MLD50 1.9–2.5 log10EID50/mL), with distinct differences in disease progression, histopathology, and organ tropism. Experimental infection of mice revealed that strain A/74/2023 induced more severe pulmonary and neurological lesions than A/75/2023. Whole-genome sequencing and phylogenetic analysis demonstrated close relatedness to HPAI H5N1 strains circulating in the Russian Far East and Japan from 2022 to 2023, with several mutations associated with mammalian adaptation, including NP-N319K and, in one isolate, PB2-E627K. According to our findings, northern fur seals (Callorhinus ursinus) on Tyuleniy Island acted as spillover hosts for the highly pathogenic avian influenza (HPAI) H5N1 virus of clade 2.3.4.4b. Furthermore, the high population density of fur seals and the extensive mortality observed during the outbreak highlight these animals’ potential role as another vessel for the evolution of avian influenza viruses. This study represents the first documented case of HPAI H5N1 in pinnipeds in the North Pacific region and supports previous reports indicating that pinnipeds, including northern fur seals, are highly susceptible to HPAI H5N1 clade 2.3.4.4b viruses.

Source: 

Link: https://www.mdpi.com/1999-4915/18/1/51

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Characterization of #H5N1 high pathogenicity avian #influenza virus belonging to clade 2.3.4.4b isolated from Ezo red #fox in #Japan in a mouse model

 

ABSTRACT

H5N1 high pathogenicity avian influenza virus (HPAIV) has spread in wild birds and poultry worldwide. H5N1 HPAIV belonging to the currently predominant clade 2.3.4.4b has infected not only birds but also mammals (wild and domestic animals), with several human infections also being reported, raising concerns for public health. In 2022, a clade 2.3.4.4b H5N1 HPAIV strain, A/Ezo red fox/Hokkaido/1/2022 (H5N1; Fox/Hok/1/22), was isolated from an Ezo red fox (Vulpes vulpes schrencki) in Hokkaido, Japan; this was the first reported case of clade 2.3.4.4b H5N1 HPAIV isolation from a mammalian species in Japan. Several amino acid substitutions in the PB2 protein play an important role in the adaptation of avian influenza viruses to mammals, but Fox/Hok/1/22 PB2 does not have any of these well-known mammalian-adapting PB2 substitutions. Here, we investigated the biological properties of Fox/Hok/1/22 in a mouse model and found that this virus was highly virulent in mice and replicated well in multiple organs, including the lungs and brain. We then examined whether viruses isolated from these organs acquired known mammalian-adapting PB2 amino acid substitutions, such as PB2 E627K. Deep sequencing analysis of viral RNA from mouse brain and lungs revealed that virus with PB2-627E was predominant in three of four mice, whereas the PB2-627K substitution was predominant in one mouse. These results indicate that Fox/Hok/1/22 is highly virulent in mice despite lacking known PB2 substitutions involved in mammalian adaptation.

IMPORTANCE

The H5N1 avian influenza virus has caused severe disease in birds worldwide and is now spreading to mammals, including humans. In 2022, this virus was detected for the first time in an Ezo red fox in Japan. To understand its potential impact on mammals, we studied this virus in mice and found that it caused severe illness, spreading to multiple organs, including the lungs and brain. Surprisingly, despite lacking genetic mutations typically associated with mammalian adaptation, the virus was highly virulent in mice. This finding suggests that the H5N1 virus may pose a greater threat to mammals, including humans, than previously thought. Given their continued spread among wild and domestic animals, our findings underscore the urgent need to monitor how recent H5N1 viruses behave in mammals.

Source: 

Link: https://journals.asm.org/doi/10.1128/spectrum.01097-25

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#Transmission, Pathological and Clinical Manifestations of Highly Pathogenic Avian #Influenza A Virus in #Mammals with Emphasis on #H5N1 Clade 2.3.4.4b

 

Abstract

Highly pathogenic avian influenza A virus (HPAIV) H5N1, clade 2.3.4.4b, has emerged as a significant zoonotic threat. H5N1 is widely circulating in wild birds, and an increasing number of spillover events have been observed in a wide range of mammalian species. These cases are primarily reported in countries on the European and American continents. This review describes the likely transmission routes, lesions, and clinical manifestations of HPAIV H5N1 clade 2.3.4.4b in naturally infected mammals, with a focus on the involvement of the central nervous system (CNS). In the analysis, pathological findings were categorized by organ system and host species, which were further divided into terrestrial mammals, marine mammals, and dairy cattle. The most frequently reported clinical manifestations were neurological and respiratory signs in marine mammals and neurological signs and lethargy in terrestrial mammals. Macroscopic and histological lesions were commonly found in the CNS and lungs of terrestrial and marine mammals, while dairy cattle showed mainly gastrointestinal and mammary gland involvement. Immunohistochemistry and reverse transcriptase real-time PCR analyses confirmed high viral loads in brain tissues, indicating a neurological tropism of H5N1 clade 2.3.4.4b. Routes of CNS invasion remain uncertain, though both hematogenous and olfactory nerve pathways are discussed. Recent evidence suggests mammal-to-mammal and vertical transmission, raising concerns for the zoonotic and pandemic potential of this virus. In conclusion, the findings emphasize an urgent need for enhanced surveillance to effectively disclose changes in viral pathogenicity and transmissibility among mammalian hosts.

Source: 

Link: https://www.mdpi.com/1999-4915/17/12/1548

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#Tissue #tropism and functional #adaptation of the #SARS-CoV-2 #spike protein in a #fatal case of #COVID19

 

ABSTRACT

Systemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to extrapulmonary tissues has been observed following acute infections. Autopsy studies further indicate tissue-specific virus diversity, including in immune-privileged sites. Questions remain on the viral dynamics leading to the tissue tropism of SARS-CoV-2, including evolutionary trajectories and functional adaptations that could impact persistence and transmission. In this study, we characterized SARS-CoV-2 genomes from 27 distinct tissues collected from an autopsy case where the patient had a primary immune deficiency. We identified tissue-specific virus genotypes, in some instances coexisting within the same sites, with mutations primarily in the receptor-binding domain of the spike protein. Protein simulations and isolation of infectious virus indicate combinations of spike substitutions that would lead to increased protein stability and stronger binding of the virus to host cells. This highlights the importance of studying patients with weakened immune responses where potential tissue reservoirs provide an environment permissive for SARS-CoV-2 evolution and diversification.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00857-25?af=R

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#SARS-CoV-2, the #human #placenta, and adverse perinatal #outcomes

Abstract

The relationship among timing and severity of COVID-19 during pregnancy, placental pathology, and adverse pregnancy outcomes is not well understood. A prospective cohort study of 497 pregnant patients with COVID-19 whose placentas underwent systematic pathologic examination was conducted. The main exposure was timing of COVID-19 during pregnancy (first/second versus third trimester). The primary outcome was composite placental pathology that included high grade maternal vascular malperfusion or greater than 25 percent perivillous fibrin deposition. There were 63 patients who had the composite placental pathology outcome. In adjusted analyses that controlled for maternal age, parity, active infection at delivery, interval from time of diagnosis to delivery and COVID-19 variant, timing of COVID-19 during pregnancy was not associated with risk of the composite placental pathology outcome. Among secondary COVID-19 related exposures that were investigated, severity of disease and treatment for COVID-19 were associated with risk of the composite placental pathology outcome. In addition, patients with COVID-19 in the first nine months of the pandemic had the highest rate of the composite placental pathology outcome. In this large cohort, placental vascular pathology was common among COVID-19 cases but was unrelated to timing of COVID-19 during pregnancy or adverse pregnancy outcomes. These findings suggest that uncomplicated COVID-19 during pregnancy does not require intensive fetal surveillance or detailed pathologic examination of the placenta after delivery.

Source: American Journal of Pathology, https://ajp.amjpathol.org/article/S0002-9440(25)00150-6/abstract?rss=yes

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#Pathology of #Influenza A (#H5N1) #infection in #pinnipeds reveals novel tissue #tropism and vertical #transmission.

Abstract

In 2023, an unprecedented outbreak of highly pathogenic avian influenza (HPAI) H5N1 resulted in the death of thousands of pinnipeds along the Argentinean coast, raising concerns about its ecological and epidemiological impact. Here, we present clinical, pathological, and molecular findings associated with HPAI H5N1 infection in pinnipeds from Chubut, Argentina. Necropsies were conducted on three South American Sea Lions (SASLs) (Otaria flavescens) and one Southern Elephant Seal (SES) (Mirounga leonina), followed by histopathological, immunohistochemical and RT-sqPCR analyses. Neurological clinical signs were observed in two SASLs, with one also exhibiting respiratory distress. Neuropathological findings included lymphoneutrophilic meningoencephalomyelitis and choroiditis, neuronal necrosis, gliosis, hemorrhages, and perivascular cuffing. Viral antigen was localized in neurons, glial cells, choroid plexus epithelial cells, ependymal cells, and the neuropil. Systemic manifestations included HPAI-related necrotizing myocarditis in the elephant seal and placental necrosis in a sea lion, with fetal tissues testing positive for HPAIV. Pulmonary lesions were minimal, limited to bronchial glands in one individual. RT-sqPCR confirmed HPAI H5 in all tested animals. Our findings highlight the neurotropism of HPAI H5N1 in pinnipeds, and expand the known systemic effects of the virus, revealing new tissue tropism and vertical transmission.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.07.636856v1

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