期刊
VIRUSES-BASEL
卷 14, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/v14091922
关键词
parvovirus B19; B19V; VP1u; receptor binding domain; PLA(2); phospholipase; thermostability; CD spectroscopy; endosomal trafficking; structure; minute virus of mice; MVM
类别
资金
- NIH R21 Grant [AI126583]
This study reveals the structural dynamics of B19V VP1u under conditions that mimic different pH values. The receptor-binding domain of VP1u exhibits an alpha-helical fold, while the PLA(2) domain exists in a molten globule state. The differences in melting temperature (T-m) at different pH values enable the virus to switch on/off the phospholipase activity during capsid trafficking. The early endosome environment is proposed as the optimal condition for endosomal escape leading to B19V infection.
Parvovirus B19 (B19V) is a human pathogen that is the causative agent of fifth disease in children. It is also known to cause hydrops in fetuses, anemia in AIDS patients, and transient aplastic crisis in patients with sickle cell disease. The unique N-terminus of Viral Protein 1 (VP1u) of parvoviruses, including B19V, exhibits phospholipase A(2) (PLA(2)) activity, which is required for endosomal escape. Presented is the structural dynamics of B19V VP1u under conditions that mimic the pHs of cell entry and endosomal trafficking to the nucleus. Using circular dichroism spectroscopy, the receptor-binding domain of B19V VP1u is shown to exhibit an alpha-helical fold, whereas the PLA(2) domain exhibits a probable molten globule state, both of which are pH invariant. Differential scanning calorimetry performed at endosomal pHs shows that the melting temperature (T-m) of VP1u PLA(2) domain is tuned to body temperature (37 degrees C) at pH 7.4. In addition, PLA(2) assays performed at temperatures ranging from 25-45 degrees C show both a temperature and pH-dependent change in activity. We hypothesize that VP1u PLA(2) domain differences in T-m at differing pHs have enabled the virus to switch on/off the phospholipase activity during capsid trafficking. Furthermore, we propose the environment of the early endosome as the optimal condition for endosomal escape leading to B19V infection.
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