ETIDIOH - NEW

  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 comple...

  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 mitigatin...

  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 ...

  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 indu...

  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 phylogeneti...

  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 rep...

  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...

  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. ...

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 an...

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 manif...