Certain low pathogenic avian influenza viruses can mutate to highly pathogenic viruses when they circulate in domestic poultry, at which point they can cause devastating poultry diseases and severe economic damage. The H7N9 influenza viruses that emerged in 2013 in China had caused severe human infections and deaths. However, these viruses were nonlethal in poultry. It is unknown whether the H7N9 viruses can acquire additional mutations during their circulation in nature and become lethal to poultry and more dangerous for humans. Here, we evaluated the evolution of H7N9 viruses isolated from avian species between 2013 and 2017 in China and found 23 different genotypes, 7 of which were detected only in ducks and were genetically distinct from the other 16 genotypes that evolved from the 2013 H7N9 viruses. Importantly, some H7N9 viruses obtained an insertion of four amino acids in their hemagglutinin (HA) cleavage site and were lethal in chickens. The index strain was not lethal in mice or ferrets, but readily obtained the 627K or 701N mutation in its PB2 segment upon replication in ferrets, causing it to become highly lethal in mice and ferrets and to be transmitted efficiently in ferrets by respiratory droplet. H7N9 viruses bearing the HA insertion and PB2 627K mutation have been detected in humans in China. Our study indicates that the new H7N9 mutants are lethal to chickens and pose an increased threat to human health, and thus highlights the need to control and eradicate the H7N9 viruses to prevent a possible pandemic.

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Protein storage vacuoles (PSVs) are unique organelles that accumulate storage proteins in plant seeds. Although morphological evidence points to the existence of multiple PSV-trafficking pathways for storage protein targeting, the molecular mechanisms that regulate these processes remain mostly unknown. Here, we report the functional characterization of the rice (Oryza sativa) glutelin precursor accumulation7 (gpa7) mutant, which over-accumulates 57-kD glutelin precursors in dry seeds. Cytological and immunocytochemistry studies revealed that the gpa7 mutant exhibits abnormal accumulation of storage pre-vacuolar compartment-like structures, accompanied by the partial mistargeting of glutelins to the extracellular space. The gpa7 mutant was altered in the CCZ1 locus, which encodes the rice homolog of Arabidopsis (Arabidopsis thaliana) CALCIUM CAFFEINE ZINC SENSITIVITY1a (CCZ1a) and CCZ1b. Biochemical evidence showed that rice CCZ1 interacts with MONENSIN SENSITIVITY1 (MON1) and that these proteins function together as the Rat brain 5 (Rab5) effector and the Rab7 guanine nucleotide exchange factor (GEF). Notably, loss of CCZ1 function promoted the endosomal localization of Vacuolar Protein Sorting-associated protein 9 (VPS9), which is the GEF for Rab5 in plants. Together, our results indicate that the MON1-CCZ1 complex is involved in post-Golgi trafficking of rice storage protein through a Rab5 and Rab7-dependent pathway.

Bats are natural reservoirs for many viruses, including several that are zoonotic. Two unusual H17N10 and H18N11 influenza viruses have been found in New World bats. Although neither of these viruses have been isolated, infectious clone technology has permitted significant progress to understand their biology, which include unique features compared to all other known influenza A viruses. In addition, an H9N2-like influenza A virus was isolated from Old World bats and it shows similar characteristics of normal influenza A viruses. In this review, current status and perspective on influenza A viruses identified in bats is reviewed and discussed.

H7N9 influenza viruses emerged in 2013 and have caused severe disease and deaths in humans in China. Some H7N9 viruses circulating in chickens have mutated to highly pathogenic viruses that have caused several disease outbreaks in chickens. Studies have shown that when the H7N9 highly pathogenic viruses replicate in ferrets or humans, they easily acquire certain mammalian-adapting mutations and become highly lethal in mice and highly transmissible in ferrets by respiratory droplet, creating the potential for human-to-human transmission. Therefore, the development of effective control measures is a top priority for H7N9 pandemic preparedness. In this study, we evaluated the protective efficacy of a cold-adapted, live attenuated H7N9 vaccine (H7N9/AAca) against two heterologous H7N9 highly pathogenic viruses in mice and guinea pigs. Our results showed that one dose of the H7N9/AAca vaccine prevented disease and death in mice challenged with two different H7N9 highly pathogenic viruses, but did not prevent replication of the challenge viruses; after two doses of H7N9/AAca, the mice were completely protected from challenge with A/chicken/Hunan/S1220/2017(H7N9) virus, and very low viral titers were detected in mice challenged with H7N9 virus CK/SD008-PB2/627 K. More importantly, we found that one dose of H7N9/AAca could efficiently prevent transmission of CK/SD008-PB2/627 K in guinea pigs. Our study suggests that H7N9/AAca has the potential to be an effective H7N9 vaccine and should be evaluated in humans.

Distinguishing hypoplastic myelodysplastic syndrome from aplastic anemia (AA) is challenging. In the present study, Japanese and Chinese pediatric hematologists and pathologists conducted a joint review of bone marrow (BM) smears and trephine biopsies in 100 children with acquired BM failure syndrome, using the criteria proposed in the 2008 edition of the World Health Organization classification of hematopoietic and lymphoid tissues. The final consensus for the diagnoses of 100 children was AA in 29 patients, refractory cytopenia of childhood (RCC) in 58 patients, and refractory cytopenia with multilineage dysplasia (RCMD) in 13 patients. No significant differences between Japanese and Chinese children were found with regards to clinical and laboratory findings, or the distribution of diagnoses. Patients with RCC/RCMD showed milder disease severity and BM hypocellularity than those with AA. To establish the provisional entities for RCC, it is essential to prospectively compare the clinical outcomes between AA and RCC groups in a large number of patients.

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