Subclinical infection without encephalitis in mice following intranasal exposure to Nipah virus-Malaysia and Nipah virus-Bangladesh

BACKGROUND: Nipah virus and Hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. In humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. Recently we reported a wild-type mouse model of Hendra virus (HeV) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mechanisms of disease recrudescence. In this study we investigated the possibility of developing a similar model of Nipah virus encephalitis. FINDINGS: Aged and young adult wild type mice did not develop clinical disease including encephalitis following intranasal exposure to either the Malaysia (NiV-MY) or Bangladesh (NiV-BD) strains of Nipah virus. However viral RNA was detected in lung tissue of mice at euthanasia (21 days following exposure) accompanied by a non-neutralizing antibody response. In a subsequent time course trial this viral RNA was shown to be reflective of an earlier self-limiting and subclinical lower respiratory tract infection through successful virus re-isolation and antigen detection in lung. There was no evidence for viremia or infection of other organs, including brain. CONCLUSIONS: Mice develop a subclinical self-limiting lower respiratory tract infection but not encephalitis following intranasal exposure to NiV-BD or NiV-MY. These results contrast with those reported for HeV under similar exposure conditions in mice, demonstrating a significant biological difference in host clinical response to exposure with these viruses. This finding provides a new platform from which to explore the viral and/or host factors that determine the neuroinvasive ability of henipaviruses

Predicting monomers for use in aqueous ring-opening metathesis polymerization-induced self-assembly

Aqueous polymerization-induced self-assembly (PISA) is a well-established methodology enabling <i>in situ</i> synthesis of polymeric nanoparticles of controllable morphology. Notably, PISA <i>via</i> ring-opening metathesis polymerization (ROMPISA) is an emerging technology for block copolymer self-assembly, mainly due to its high versatility and robustness. However, a limited number of monomers suitable for core-forming blocks in aqueous ROMPISA have been reported to date. In this work, we identified seven monomers for use as either corona- or core-forming blocks during aqueous ROMPISA by <i>in silico</i> calculation of relative hydrophobicity for corresponding oligomeric models. The predicted monomers were validated experimentally by conducting ROMPISA using our previously reported two-step approach. In addition to predictive data, our computational model was exploited to identify trends between polymer hydrophobicity and the morphology of the self-assembled nano-objects they formed. We expect that this methodology will greatly expand the scope of aqueous ROMPISA, as monomers can be easily identified based on the structure–property relationships observed herein

DNA-polymer conjugates via the graft-through polymerisation of native DNA in water

The direct, graft-through, ring-opening metathesis polymerisation (ROMP) of unprotected DNA macromonomers is reported. By tuning the polymerisation conditions, good control is achieved, enabling the rapid and efficient synthesis of DNA-containing bottlebrush copolymers, without the need for protection of the DNA bases

The Nature of Exposure Drives Transmission of Nipah Viruses from Malaysia and Bangladesh in Ferrets.

Person-to-person transmission is a key feature of human Nipah virus outbreaks in Bangladesh. In contrast, in an outbreak of Nipah virus in Malaysia, people acquired infections from pigs. It is not known whether this important epidemiological difference is driven primarily by differences between NiV Bangladesh (NiV-BD) and Malaysia (NiV-MY) at a virus level, or by environmental or host factors. In a time course study, ferrets were oronasally exposed to equivalent doses of NiV-BD or NiV-MY. More rapid onset of productive infection and higher levels of virus replication in respiratory tract tissues were seen for NiV-BD compared to NiV-MY, corroborating our previous report of increased oral shedding of NiV-BD in ferrets and suggesting a contributory mechanism for increased NiV-BD transmission between people compared to NiV-MY. However, we recognize that transmission occurs within a social and environmental framework that may have an important and differentiating role in NiV transmission rates. With this in mind, ferret-to-ferret transmission of NiV-BD and NiV-MY was assessed under differing viral exposure conditions. Transmission was not identified for either virus when naïve ferrets were cohoused with experimentally-infected animals. In contrast, all naïve ferrets developed acute infection following assisted and direct exposure to oronasal fluid from animals that were shedding either NiV-BD or NiV-MY. Our findings for ferrets indicate that, although NiV-BD may be shed at higher levels than NiV-MY, transmission risk may be equivalently low under exposure conditions provided by cohabitation alone. In contrast, active transfer of infected bodily fluids consistently results in transmission, regardless of the virus strain. These observations suggest that the risk of NiV transmission is underpinned by social and environmental factors, and will have practical implications for managing transmission risk during outbreaks of human disease

Transmission Routes for Nipah Virus from Malaysia and Bangladesh

Bangladesh are associated with markedly different patterns of transmission and pathogenicity. To compare the 2 strains, we conducted an in vivo study in which 2 groups of ferrets were oronasally exposed to either the Malaysia or Bangladesh strain of Nipah virus. Viral shedding and tissue tropism were compared between the 2 groups. Over the course of infection, significantly higher levels of viral RNA were recovered from oral secretions of ferrets infected with the Bangladesh strain. Higher levels of oral shedding of the Bangladesh strain of Nipah virus might be a key factor in onward transmission in outbreaks among humans. Nipah virus (NiV), a bat-borne paramyxovirus, has caused outbreaks of human disease with high mortalit