The continued detection of zoonotic viral infections in bats has led to the microbial fauna of these mammals being studied at a greater level than ever before. Whilst numerous pathogens have been discovered in bat species, infection with lyssaviruses is of particular significance from a zoonotic perspective as, where human infection has been reported, it is invariably fatal. Here we review the detection of lyssaviruses within different bat species and overview what is understood regarding their maintenance and transmission following both experimental and natural infection. We discuss the relevance of these pathogens as zoonotic agents and the threat of newly discovered viruses to human populations.

An early and yet indispensable step in the alphaherpesvirus infection is the engagement of host receptors by the viral envelope glycoprotein D (gD). Of the thus-far identified gD receptors, nectin-1 is likely the most effective in terms of its wide usage by multiple alphaherpesviruses for cell entry. The molecular basis of nectin-1 recognition by the gD protein is therefore an interesting scientific question in the alphaherpesvirus field. Previous studies focused on the herpes simplex virus (HSV) of the Simplexvirus genus, for which both the free gD structure and the gD/nectin-1 complex structure were reported at high resolutions. The structural and functional features of other alphaherpesviral gDs, however, remain poorly characterized. In the current study, we systematically studied the characteristics of nectin-1 binding by the gD of a Varicellovirus genus member, the pseudorabies virus (PRV). We first showed that PRV infects host cells via both human and swine nectin-1, and that its gD exhibits similar binding affinities for nectin-1 of the two species. Furthermore, we demonstrated that removal of the PRV gD membrane-proximal residues could significantly increase its affinity for the receptor binding. The structures of PRV gD in the free and the nectin-1-bound states were then solved, revealing a similar overall 3D fold as well as a homologous nectin-1 binding mode to its HSV counterpart. However, several unique features were observed at the binding interface of PRV gD, enabling the viral ligand to utilize different gD residues (from those of HSV) for nectin-1 engagement. These observed binding characteristics were further verified by the mutagenesis study using the key-residue mutants of nectin-1. The structural and functional data obtained in this study, therefore, provide the basis of receptor recognition by PRV gD. Both herpes simplex virus (HSV) and pseudorabies virus (PRV) recognize nectin-1 as the cellular receptor. They utilize the envelope glycoprotein D (gD) on the virion surface to interact with nectin-1, initiating the virus infection. Although the molecular basis of nectin-1 binding by HSV gD has been successfully elucidated with high resolution structures, the atomic features of PRV gD interacting with the same receptor remains uncharacterized. Here, we show that PRV gD exhibits nano-molar affinities for both human and swine nectin-1, and deletion of the membrane-proximal loop in the gD ectodomain dramatically increases its receptor-binding avidity. We further solved the free and the nectin-1-bound PRV gD structures. The free gD structure reveals a canonical fold of an IgV-like core wrapped by the N- and C-terminal extensions as observed in the HSV homologs. The N-terminus of PRV gD, however, is shorter than that of HSV gDs. The solved complex structure demonstrates that PRV gD exhibits a homologous receptor-binding mode to the HSV counterpart. Nevertheless, several unique features at the PRV gD binding interface suffice the viral ligand to engage nectin-1 with a series of residues differing from the HSV amino acids. These observations not only delineated the molecular basis of PRV engaging nectin-1 but also enriched our knowledge on the receptor-binding mechanism of the Alphaherpesvirinae subfamily.

Viperin (virus inhibitory protein, endoplasmic reticulum-associated, IFN-inducible) is an interferon-inducible protein that mediates antiviral activity. Generally, rabies virus (RABV) multiplies extremely well in susceptible cells, leading to high virus titres. In this study, we found that viperin was significantly up-regulated in macrophage RAW264.7 cells but not in NA, BHK-21 or BSR cells. Transient viperin overexpression in BSR cells and stable expression in BHK-21 cells could inhibit RABV replication, including both attenuated and street RABV. Furthermore, the inhibitory function of viperin was related to reduce cholesterol/sphingomyelin on the membranes of RAW264.7 cells. We explored the up-stream regulation pathway of viperin in macrophage RAW264.7 cells in the context of RABV infection. An experiment confirmed that a specific Toll-like receptor 4 (TLR4) inhibitor, TAK-242, could inhibit viperin expression in RABV-infected RAW264.7 cells. These results support a regulatory role for TLR4. Geldanamycin, a specific inhibitor of interferon regulatory factor 3 (IRF3) (by inhibiting heat-shock protein 90 (Hsp90) of the IRF3 phosphorylation chaperone), significantly delayed and reduced viperin expression, indicating that IRF3 is involved in viperin induction in RAW264.7 cells. Taken together, our data support the therapeutic potential for viperin to inhibit RABV replication, which appears to involve upstream regulation by TLR4.

Mycoplasma synoviae (M. synoviae) is widely distributed around the world, and leads to serious economic losses in the world every year. Nevertheless, the incidence and epidemiology of M. synoviae infection in China have remained unclear. In this study we demonstrate that over 9773 broiler chicken flocks in 16 Chinese provinces were affected by M. synoviae between 2010 and 2015. Our epidemiological study revealed that M. synoviae was widely prevalent in multi-aged Chinese native breeder chickens, and the prevalence of M. synoviae in embryos of breeders reached up to 16.29%. In addition, our data showed that chickens aged 14 days or younger carried simultaneously high levels of maternal antibody against M. synoviae and high M. synoviae infection (10%), and low M. synoviae antibody levels in breeders and high proportion of M. synoviae infection in embryos could increase the chances of incidence in the offspring. Finally, our results also indicated that 3- to 7-week-old chickens might be most the susceptible to M. synoviae and, therefore, might play a key role in the horizontal transmission of M. synoviae. Our findings suggest that M. synoviae is widely circulating in Chinese native chickens, accordingly, effective control measures are urgently needed to control the spread.

Influenza viruses pose a significant threat to human health. They are responsible for a large number of deaths annually and have a serious impact on the global economy. There are numerous influenza virus subtypes, antigenic variations occur continuously, and epidemic trends are difficult to predict—all of which lead to poor outcomes of routine vaccination against targeted strain subtypes. Therefore, the development of universal influenza vaccines still constitutes the ideal strategy for controlling influenza. This article reviews the progress in development of universal vaccines directed against the conserved regions of hemagglutinin (HA), neuraminidase (NA), and other structural proteins of influenza viruses using new technologies and strategies with the goals of enhancing our understanding of universal influenza vaccines and providing a reference for research into the exploitation of natural immunity against influenza viruses.