Integrated clinical, pathologic, virologic, and transcriptomic analysis of H5N1 influenza virus-induced viral pneumonia in the rhesus macaque.

Viral pneumonia has been frequently reported during early stages of influenza virus pandemics and in many human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection. To better understand the pathogenesis of this disease, we produced nonlethal viral pneumonia in rhesus macaques by using an HPAI H5N1 virus (A/Anhui/2/2005; referred to as Anhui/2). Infected macaques were monitored for 14 days, and tissue samples were collected at 6 time points for virologic, histopathologic, and transcriptomic analyses. Anhui/2 efficiently replicated in the lung from 12 h to 3 days postinfection (p.i.) and caused temporal but severe pneumonia that began to resolve by day 14. Lung transcriptional changes were first observed at 6 h, and increased expression of vascular permeability regulators and neutrophil chemoattractants correlated with increased serum leakage and neutrophil infiltration in situ. Additional inflammatory, antiviral, and apoptotic genes were upregulated from 12 h, concurrent with viral antigen detection and increasing immune cell populations. A shift toward upregulation of acquired immunity was apparent after day 6. Expression levels of established immune cell molecular markers revealed remarkable similarity with pathological findings, indicating early and robust neutrophil infiltration, a slight delay in macrophage accumulation, and abundant late populations of T lymphocytes. We also characterized the putative mechanisms regulating a unique, pneumonia-associated biphasic fever pattern. Thus, this study is the first to use a comprehensive and integrative approach to delineate specific molecular mechanisms regulating influenza virus-induced pneumonia in nonhuman primates, an important first step toward better management of human influenza virus disease.

Outstanding reinforcing effect of highly oriented chitin whiskers in PVA nanocomposites.

To utilize the extreme reinforcing performance of chitin whiskers (ChWs), the current work was undertaken to fabricate nanocomposites embedded with highly uniaxial oriented ChWs into the matrix polymer. Fibers of poly(vinyl alcohol) (PVA)/ChWs were prepared by gel spinning and the fibers were subjected to a hot drawing to their maximal draw ratio. WAXD analysis revealed the very high orientation of ChWs in the PVA matrix. DSC measurements showed that, upon ChWs loadings, crystallinity of PVA increased and non-isothermal cooling crystallization peak of PVA shifted towards lower temperature, indicating the interaction of PVA with ChWs. Measurement of infrared dichroism suggested that the orientation of overall PVA chains increased with the increase in ChWs loading due to the possible dragging of PVA chains attached with ChWs during drawing, which resulted higher PVA crystallinity in the composites. The stress transfer in PVA/ChWs interface quantified by X-ray diffraction evidenced the strong adherence between the two. The stress transfer between PVA and ChWs interface, and higher PVA crystallinity induced by ChWs were reflected to the outstanding enhancement in mechanical- and anti-creep properties of nanocomposite fibers.