Author Contributions: Drs Liu and Yang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Dong and Tian contributed equally to the study. Drs Liu and Yang contributed equally as senior authors.

The pandemic influenza virus of 1918–1919 killed an estimated 20 to 50 million people worldwide. With the recent availability of the complete 1918 influenza virus coding sequence, we used reverse genetics to generate an influenza virus bearing all eight gene segments of the pandemic virus to study the properties associated with its extraordinary virulence. In stark contrast to contemporary human influenza H1N1 viruses, the 1918 pandemic virus had the ability to replicate in the absence of trypsin, caused death in mice and embryonated chicken eggs, and displayed a high-growth phenotype in human bronchial epithelial cells. Moreover, the coordinated expression of the 1918 virus genes most certainly confers the unique high-virulence phenotype observed with this pandemic virus.

Recent reports of mild to severe influenza-like illness in humans caused by a novel swine-origin 2009 A(H1N1) influenza virus underscore the need to better understand the pathogenesis and transmission of these viruses in mammals. In this study, selected 2009 A(H1N1) influenza isolates were assessed for their ability to cause disease in mice and ferrets and compared with a contemporary seasonal H1N1 virus for their ability to transmit to naïve ferrets through respiratory droplets. In contrast to seasonal influenza H1N1 virus, 2009 A(H1N1) influenza viruses caused increased morbidity, replicated to higher titers in lung tissue, and were recovered from the intestinal tract of intranasally inoculated ferrets. The 2009 A(H1N1) influenza viruses exhibited less efficient respiratory droplet transmission in ferrets in comparison with the highly transmissible phenotype of a seasonal H1N1 virus. Transmission of the 2009 A(H1N1) influenza viruses was further corroborated by characterizing the binding specificity of the viral hemagglutinin to the sialylated glycan receptors (in the human host) by use of dose-dependent direct receptor-binding and human lung tissue-binding assays.

On 29 March 2013, the Chinese Center for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A(H7N9) virus. The recent human infections with H7N9 virus, totalling over 130 cases with 39 fatalities to date, have been characterized by severe pulmonary disease and acute respiratory distress syndrome (ARDS). This is concerning because H7 viruses have typically been associated with ocular disease in humans, rather than severe respiratory disease. This recent outbreak underscores the need to better understand the pathogenesis and transmission of these viruses in mammals. Here we assess the ability of A/Anhui/1/2013 and A/Shanghai/1/2013 (H7N9) viruses, isolated from fatal human cases, to cause disease in mice and ferrets and to transmit to naive animals. Both H7N9 viruses replicated to higher titre in human airway epithelial cells and in the respiratory tract of ferrets compared to a seasonal H3N2 virus. Moreover, the H7N9 viruses showed greater infectivity and lethality in mice compared to genetically related H7N9 and H9N2 viruses. The H7N9 viruses were readily transmitted to naive ferrets through direct contact but, unlike the seasonal H3N2 virus, did not transmit readily by respiratory droplets. The lack of efficient respiratory droplet transmission was corroborated by low receptor-binding specificity for human-like α2,6-linked sialosides. Our results indicate that H7N9 viruses have the capacity for efficient replication in mammals and human airway cells and highlight the need for continued public health surveillance of this emerging virus.

Most of the existing learning-based single image super-resolution (SISR) methods are trained and evaluated on simulated datasets, where the low-resolution (LR) images are generated by applying a simple and uniform degradation (i.e., bicubic downsampling) to their high-resolution (HR) counterparts. However, the degradations in real-world LR images are far more complicated. As a consequence, the SISR models trained on simulated data become less effective when applied to practical scenarios. In this paper, we build a real-world super-resolution (RealSR) dataset where paired LR-HR images on the same scene are captured by adjusting the focal length of a digital camera. An image registration algorithm is developed to progressively align the image pairs at different resolutions. Considering that the degradation kernels are naturally non-uniform in our dataset, we present a Laplacian pyramid based kernel prediction network (LP-KPN), which efficiently learns per-pixel kernels to recover the HR image. Our extensive experiments demonstrate that SISR models trained on our RealSR dataset deliver better visual quality with sharper edges and finer textures on real-world scenes than those trained on simulated datasets. Though our RealSR dataset is built by using only two cameras (Canon 5D3 and Nikon D810), the trained model generalizes well to other camera devices such as Sony a7II and mobile phones.

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Retinoic acid-inducible gene I (RIG-I) has recently been identified as one of the key intracellular sensors of virus infection. RIG-I binds to cytosolic double-stranded RNA and initiates a signaling cascade that leads to the activation of transcription factors required for expression of type I interferon (IFN-I). Previous evidence suggests that nonstructural protein 1 (NS1) encoded by influenza A virus (IAV) suppresses IFN-I secretion in virus-infected cells by an unknown mechanism. In the present study, we demonstrate that RIG-I is required

The influenza virus genes that confer efficient transmission of epidemic and pandemic strains in humans have not been identified. The rapid spread and severe disease caused by the 1918 influenza pandemic virus makes it an ideal virus to study the transmissibility of potentially pandemic influenza strains. Here, we used a series of human 1918-avian H1N1 influenza reassortant viruses to identify the genetic determinants that govern airborne transmission of avian influenza viruses. We have demonstrated that the 1918 HA gene was necessary for efficient direct contact transmission, but did not allow respiratory droplet transmission between ferrets of an avian influenza virus possessing an avian polymerase subunit PB2. The 1918 PB2 protein was found to be both necessary and sufficient for airborne transmission of a virus expressing the 1918 HA and neuraminidase. Also, it was found that influenza viruses that were able to transmit efficiently in ferrets were able to replicate efficiently at the lower temperature (33°C) found in the environment of mammalian airway. These findings demonstrate that the adaptation of the HA and PB2 proteins are critical for the development of pandemic influenza strains from avian influenza viruses. ferrets ͉ 1918 pandemic