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Endosymbionts modulate virus effects on aphid-plant interactions
Vector-borne pathogens frequently modify traits of their primary hosts and vectors in ways that influence disease transmission. Such effects can themselves be altered by the presence of other microbial symbionts, yet we currently have limited understanding of these interactions. Here we show that effects of pea enation mosaic virus (PEMV) on interactions between host plants and aphid vectors are modulated by the presence of different aphid endosymbionts. In a series of laboratory assays, we found strong interactive effects of virus infection and endosymbionts on aphid metabolomic profiles, population growth, behavior, and virus transmission during aphid feeding. Furthermore, the strongest effects—and those predicted to favor virus transmission—were most apparent in aphid lines harboring particular endosymbionts. These findings show that virus effects on host-vector interactions can be strongly influenced by other microbial symbionts and suggest a potentially important role for such interactions in disease ecology and evolution.
Recruitment of apolipoprotein E facilitates Herpes simplex virus 1 attachment and release
Human apolipoprotein E (ApoE) has been shown to play important roles during primary infection and pathogenesis of several viruses. Furthermore, epidemiological studies suggest that interactions between ApoE 4 and herpes simplex virus type-1 (HSV1) could associate with higher risk of Alzheimer’s disease. Nevertheless, little is known about the ApoE-HSV1 interactions at molecular levels. Here, we investigate the effects of ApoE on HSV1 infection in vitro. Our results show that ApoE promotes HSV1 growth, which is attributed to the incorporation of ApoE into HSV1 particles. Using both biological and biophysical approaches, we conclude that ApoE-coated HSV1 demonstrates a more efficient attachment to and faster release from the cell surface. Mechanistic studies reveal that ApoE modifies HSV1 interactions with heparan sulfate, thereby modulating interactions between HSV1 and the cell surface. Overall, our results provide new insights into the roles of ApoE during HSV1 infections which may inspire future studies on Alzheimer’s disease etiology.
Pathogenesis and transmission of SARS-CoV-2 D614G, Alpha, Gamma, Delta, and Omicron variants in golden hamsters
Since the emergence of SARS-CoV-2 in humans, novel variants have evolved to become dominant circulating lineages. These include D614G (B.1 lineage), Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2), and Omicron BA.1 (B.1.1.529) and BA.2 (B.1.1.529.2) viruses. Here, we compared the viral replication, pathogenesis, and transmissibility of these variants. Replication kinetics and innate immune response against the viruses were tested in ex vivo human nasal epithelial cells (HNEC) and induced pluripotent stem cell-derived lung organoids (IPSC-LOs), and the golden hamster model was employed to test pathogenicity and potential for transmission by the respiratory route. Delta, BA.1, and BA.2 viruses replicated more efficiently, and outcompeted D614G, Alpha, and Gamma viruses in an HNEC competition assay. BA.1 and BA.2 viruses, however, replicated poorly in IPSC-LOs compared to other variants. Moreover, BA.2 virus infection significantly increased secretion of IFN-λ1, IFN-λ2, IFN-λ3, IL-6, and IL-1RA in HNECs relative to D614G infection, but not in IPSC-LOs. The BA.1 and BA.2 viruses replicated less effectively in hamster lungs compared to the other variants; and while the Gamma virus reached titers comparable to D614G and Delta viruses, it caused greater lung pathology. Lastly, the Gamma and Delta variants transmitted more efficiently by the respiratory route compared to the other viruses, while BA.1 and BA.2 viruses transmitted less efficiently. These findings demonstrate the ongoing utility of experimental risk assessment as SARS-CoV-2 variants continue to evolve.
Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines
The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. The integration of novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, and artificial intelligence have significantly expedited the development of groundbreaking peptide-based drugs, effectively addressing the obstacles associated with their character, such as the rapid clearance and degradation, necessitating subcutaneous injection leading to increasing patient discomfort, and ultimately advancing translational research efforts. Peptides are presently employed in the management and diagnosis of a diverse array of medical conditions, such as diabetes mellitus, weight loss, oncology, and rare diseases, and are additionally garnering interest in facilitating targeted drug delivery platforms and the advancement of peptide-based vaccines. This paper provides an overview of the present market and clinical trial progress of peptide-based therapeutics, delivery platforms, and vaccines. It examines the key areas of research in peptide-based drug development through a literature analysis and emphasizes the structural modification principles of peptide-based drugs, as well as the recent advancements in screening, design, and delivery technologies. The accelerated advancement in the development of novel peptide-based therapeutics, including peptide-drug complexes, new peptide-based vaccines, and innovative peptide-based diagnostic reagents, has the potential to promote the era of precise customization of disease therapeutic schedule.
Dominant HPAIV H5N1 genotypes of Germany 2021/2022 are linked to high virulence in Pekin ducklings
Highly pathogenic avian influenza viruses (HPAIV) of H5 clade 2.3.4.4b pose an ongoing threat worldwide. It remains unclear whether this panzootic situation would favor low virulent phenotypes expected by the ‘avirulence hypothesis’ of viral evolution. Assessing virulence in Pekin ducklings in an intramuscular infection model revealed that the two genotypes that dominated the epidemiological situation in Germany during the period 2021 and 2022 (EU-RL:CH and EU-RL:AB) were of high virulence. In contrast, rare genotypes were of intermediate virulence. The genetic constellation of these reassortants pointed to an important role of the viral polymerase complex (RdRP), particularly the PB1 genome segment, in shaping virulence in ducklings. Occulo-nasal infection of ducklings confirmed the phenotypes for two representative viruses and indicated a more efficient replication for the high virulence strain. These observations would be in line with the ‘virulence-transmission trade-off’ model for describing HPAIV epidemiology in wild birds in Germany.
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