Bub1 Facilitates Virus Entry through Endocytosis in a Model of Drosophila Pathogenesis

Abstract

In this work, we identify for the first time that the nuclear protein Bub1 (budding uninhibited by benzimidazoles 1), a highly conserved subunit of the kinetochore complex regulating chromosome congression, has a novel and important function on the cell membrane to facilitate the virus to enter host cells. Bub1 deficiency empowers the host to have the ability to resist viral infection in Drosophila and a human cell line. Bub1 is involved in the virus entry step through regulating endocytosis. The DCV capsid protein can recruit Bub1, and DCV infection can strengthen the interaction between Bub1 and a clathrin-dependent endocytosis component. The restricted entry of vesicular stomatitis virus (VSV) and Listeria monocytogenes in bub1-deficient flies and cell lines was also observed. Therefore, our data implicate a previously unknown function of Bub1 that can be hijacked by pathogens to facilitate their entry, and Bub1 may serve as a potential antiviral therapy target for limiting viral entry.

Functional reciprocity of proteins involved in mitosis and endocytosis

“…Another related discovery in Drosophila that links the MCC to endocytosis is that Bub1, the protein kinase catalyzes the MCC assembly in mitosis, has been identified in a survival screen upon Drosophila C virus (DCV) infection. Bub1 mutant flies become resistant to DCV because it has a compromised CME pathway [102]. This result implies that more components in the SAC might contribute to the regulation of CME in interphase.…”

Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance

“…These data argue that tight regulation of JAK/Stat signaling is essential to maintain proper muscle function. Over the past several years the power of Drosophila to characterize inter-organ communication pathways (Rai et al, 2021; Robles-Murguia et al, 2020; Yang et al, 2019), and to identify pathogenic mechanisms driving infectious disease (Adamson et al, 2011; Chan et al, 2009; Hao et al, 2008; Harsh et al, 2020; Hughes et al, 2012; Liu et al, 2018; Yang et al, 2018) has come to light. We used Drosophila to investigate a putative brain-muscle signaling, and found neuroinflammation activates the brain-muscle axis and regulates muscle performance.…”

Analysis and identification of potential type II helper T cell (Th2)-Related key genes and therapeutic agents for COVID-19

“…Aberrant expression of BUB1 affects the function of the spindle checkpoint, resulting in chromosomal instability during mitosis. BUB1 also plays an important role in virus entry [ 75 ]. UBE2C is a member of the E2 family of ubiquitin-conjugating enzymes that plays an important role in cellular regulation by specifically binding to late cell cycle facilitation complexes.…”