We have generated a recombinant Newcastle disease virus (NDV) that expresses the green fluorescence protein (GFP) in infected chicken embryo fibroblasts (CEFs). This virus is interferon (IFN

Both antibodies and T cells contribute to immunity against influenza virus infection. However

Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.

). We now show that the NDV V protein plays an important role in host range restriction. In order to study V functions in vivo, recombinant NDV (rNDV) mutants, defective in the expression of the V protein, were generated. These rNDV mutants grow poorly in both embryonated chicken eggs and chicken embryo fibroblasts (CEFs) compared to the wild-type (wt) rNDV. However, insertion of the NS1 gene of influenza virus A/PR8/34 into the NDV V(؊) genome [rNDV V(؊)/NS1] restores impaired growth to wt levels in embryonated chicken eggs and CEFs. These data indicate that for viruses infecting avian cells, the NDV V protein and the influenza NS1 protein are functionally interchangeable, even though there are no sequence similarities between the two proteins. Interestingly, in human cells, the titer of wt rNDV is 10 times lower than that of rNDV V(؊)/NS1. Correspondingly, the level of IFN secreted by human cells infected with wt rNDV is much higher than that secreted by cells infected with the NS1-expressing rNDV. This suggests that the IFN antagonist activity of the NDV V protein is species specific. Finally, the NDV V protein plays an important role in preventing apoptosis in a species-specific manner. The rNDV defective in V induces apoptotic cell death more rapidly in CEFs than does wt rNDV. Taken together, these data suggest that the host range of NDV is limited by the ability of its V protein to efficiently prevent innate host defenses, such as the IFN response and apoptosis.Newcastle disease virus (NDV), an avian paramyxovirus, is classified as the only member of the genus Avulavirus belonging to the family Paramyxoviridae within the order Mononegavirales (http://www.ictvdb.iacr.ac.uk/Ictv/fr-fst-a.htm). NDV is an economically important pathogen, since periodic outbreaks affect the poultry industry. NDV is also considered a potential oncolytic agent in the treatment of cancer because it can selectively kill tumor cells (29). NDV isolates are categorized as velogenic (highly virulent), mesogenic (intermediate), or lentogenic (nonvirulent), depending on the severity of the disease they cause (2). A critical molecular determinant for the pathogenicity of NDV appears to be the cleavage site of the fusion (F) protein (20).The NDV genome is 15,186 nucleotides long, and it consists of six transcriptional units that encode the nucleocapsid protein (NP), phosphoprotein (P), matrix protein (M), F protein, hemagglutinin protein (HN), and the polymerase protein (L). Two additional proteins, V and W, are expressed by mRNAs, which are derived from the P gene via RNA editing (26,30,31). These V and W proteins share their amino (N)-terminal domains with the P protein and vary at their carboxy (C) termini. The NDV V protein, similar to other paramyxovirus V proteins, has a cysteine-rich C-terminal domain which binds two atoms of Zn 2ϩ (30). It has been demonstrated that plasmid-mediated expression of the NDV V protein or of its C-terminal domain inhibits the alpha/beta interferon (IFN-␣/␤) response (19). We now show, using reverse gene...

Avian influenza viruses of the H5 and H7 hemagglutinin subtypes, and Newcastle disease virus (NDV), are important pathogens in poultry worldwide. Specifically, the highly pathogenic H5N1 avian influenza virus is a particular threat because it has now occurred in more than 40 countries on several continents. Inasmuch as most chickens worldwide are vaccinated with a live NDV vaccine, we embarked on the development of vaccine prototypes that would have dual specificity and would allow a single immunization against both avian influenza and Newcastle disease. Using reverse genetics, we constructed a chimeric avian influenza virus that expressed the ectodomain of the hemagglutinin-neuraminidase gene of NDV instead of the neuraminidase protein of the H5N1 avian influenza virus. Our second approach to creating a bivalent vaccine was based on expressing the ectodomain of an H7 avian influenza virus hemagglutinin in a fusogenic and attenuated NDV background. The insertion into the NDV genome of the foreign gene (containing only its ectodomain, with the transmembrane and cytoplasmic domains derived from the F protein of NDV) resulted in a chimeric virus with enhanced incorporation of the foreign protein into virus particles. A single immunization of chickens with this improved vaccine prototype virus induced not only a 90% protection against an H7N7 highly pathogenic avian influenza virus, but also complete immunity against a highly virulent NDV. We propose that chimeric constructs should be developed for convenient, affordable, and effective vaccination against avian influenza and Newcastle disease in chickens and other poultry.chicken ͉ Newcastle disease virus ͉ pandemic ͉ avian influenza virus ͉ hemagglutinin