HSC70 is required for infectious bursal disease virus (IBDV) infection in DF-1 cells

Infectious bursal disease (IBD) is a highly epidemic and immunosuppressive disease of 3- to 6-week-old chicks caused by infectious bursal disease virus (IBDV). Since 2017, there has been a notable increase in the isolation rates of novel variant IBDV strains in China, of which characteristic amino acid residues were different from those of early antigen variants. In this study, one IBDV strain was isolated from a farm with suspected IBD outbreak in Shandong Province, China, which was designated LY21/2. The strain LY21/2 could replicate in MC38 cells with previous culture adaption in SPF chick embryos. Phylogenetic analysis revealed that LY21/2 formed one branch with novel variant IBDVs and shared 96.8–98.6% nucleotide sequence identity with them. Moreover, LY21/2 serving as the major parent underwent the recombination event of a variant strain (19D69), while the minor parent was a very virulent strain (Harbin-1). SPF chicks inoculated with LY21/2 showed no gross clinic symptom, whereas bursal atrophy was exhibited and apoptosis was occurred in 55.21% of bursal cells. The results of histopathology and immunohistochemical staining showed that lymphocyte depletion and connective tissue hyperplasia and IBDV antigen-positive cells were observed in the bursa of LY21/2-infected chicks. Besides, DNA fragmentation was detected in the LY21/2-infected bursal tissue section by TUNEL assay. Collectivtely, these data presented analysis and evaluation of the genetic characteristics and pathogenicity of a novel variant IBDV strain. This study may help in the development of biosafety strategies for the prevention and control of IBDV in poultry.

Section: Discussionmentioning

confidence: 99%

Characterization and pathogenicity of a novel variant infectious bursal disease virus in China

Huang

Shu²,

Cong³

et al. 2023

“…Studies have shown that the tylophorine analog, such as DCB-3503 and rac-cryptopleurine, specifically binds to the NBD of HSC70 and stimulates ATP hydrolysis in the presence of the poly U/UC motif of HCV RNA and thus inhibits viral translation consequently (Wang et al, 2018). As an ATP analog, adenosine derivative compound VER-155008 acts as a competitive inhibitor to bind the HSP70 family and induces conformational changes of HSC70, making it impossible for HSC70 to interact with infectious bursal disease virus (IBDV) VP2 protein and eventually inhibiting virus replication (Chen et al, 2020). Therefore, HSC70 is a promising target for antivirals and needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

Mechanism and Complex Roles of HSC70 in Viral Infections

Wang

Yang

et al. 2020

Heat shock cognate 71-kDa protein (HSC70), a constitutively expressed molecular chaperon within the heat shock protein 70 family, plays crucial roles in maintaining cellular environmental homeostasis through implicating in a wide variety of physiological processes, such as ATP metabolism, protein folding and transporting, antigen processing and presentation, endocytosis, and autophagy. Notably, HSC70 also participates in multiple non-communicable diseases and some pathogen-caused infectious diseases. It is known that virus is an obligatory intracellular parasite and heavily relies on host machineries to self-replication. Undoubtedly, HSC70 is a striking target manipulated by virus to ensure the successful propagation. In this review, we summarize the recent advances of the regulatory mechanisms of HSC70 during viral infections, which will be conducive to further study viral pathogenesis.

“…Similarly, a selective HSC70 inhibitor, oxymatrine, suppresses de novo synthesis of both the wild-type HBV strain and strains resistant to 3TC, ADV, and ETV, presumably through destabilization of Hsc70 mRNA ( Gao et al, 2011 ). As an ATP analog, adenosine derivative compound VER-155008 acts as a competitive inhibitor to bind the HSP70 family and induces the conformational changes of HSC70, making it impossible for HSC70 to interact with IBDV VP2 protein and thus inhibiting virus replication ( Chen et al, 2020 ).…”

Section: Antiviral Therapy By Targeting Selective Autophagymentioning

confidence: 99%

Targeting Selective Autophagy as a Therapeutic Strategy for Viral Infectious Diseases

Zhou

et al. 2022

Autophagy is an evolutionarily conserved lysosomal degradation system which can recycle multiple cytoplasmic components under both physiological and stressful conditions. Autophagy could be highly selective to deliver different cargoes or substrates, including protein aggregates, pathogenic proteins or superfluous organelles to lysosome using a series of cargo receptor proteins. During viral invasion, cargo receptors selectively target pathogenic components to autolysosome to defense against infection. However, viruses not only evolve different strategies to counteract and escape selective autophagy, but also utilize selective autophagy to restrict antiviral responses to expedite viral replication. Furthermore, several viruses could activate certain forms of selective autophagy, including mitophagy, lipophagy, aggrephagy, and ferritinophagy, for more effective infection and replication. The complicated relationship between selective autophagy and viral infection indicates that selective autophagy may provide potential therapeutic targets for human infectious diseases. In this review, we will summarize the recent progress on the interplay between selective autophagy and host antiviral defense, aiming to arouse the importance of modulating selective autophagy as future therapies toward viral infectious diseases.