establishment-viral-infection-analysis-host-virus-interaction

Establishment of Viral Infection and Analysis of Host-Virus Interaction in <em>Drosophila Melanogaster</em>

Virus spreading is a major cause of epidemic diseases. Thus, understanding the interaction between the virus and the host is very important to extend our ...

Guangzhou Women and Children's medical center

Chinese Academy of Sciences

Guangzhou Women and Children's Medical Center

Immune homeostasis is a prerequisite to protective immunity against gastrointestinal infections. In Drosophila, immune deficiency (IMD) signalling (tumour necrosis factor receptor/interleukin-1 receptor, TNFR/IL-1R in mammals) is indispensable for intestinal immunity against invading bacteria. However, how this local antimicrobial immune response contributes to inflammatory regulation remains poorly defined. Here, we show that flies lacking intestinal Bap180 (a subunit of the chromatin-remodelling switch/sucrose non-fermentable (SWI/SNF) complex) are susceptible to infection as a result of hyper-inflammation rather than bacterial overload. Detailed analysis shows that Bap180 is induced by the IMD-Relish response to both enteropathogenic and commensal bacteria. Upregulated Bap180 can feed back to restrain overreactive IMD signalling, as well as to repress the expression of the pro-inflammatory gene eiger (TNF), a critical step to prevent excessive tissue damage and elongate the lifespan of flies, under pathological and physiological conditions, respectively. Furthermore, intestinal targeting of Baf180 renders mice susceptible to a more aggressive infectious colitis caused by Citrobacter rodentium. Together, Bap180 and Baf180 serve as a conserved transcriptional repressor that is critical for the maintenance of innate immune homeostasis in the intestines.

Bap180/Baf180 is required to maintain homeostasis of intestinal innate immune response in Drosophila and mice.

In order to establish productive infection and dissemination, viruses usually evolve a number of strategies to hijack and/or subvert the host defense systems. However, host factors utilized by the virus to facilitate infection remain poorly characterized. In this work, we found that  deficient in  (), a highly conserved subunit of the kinetochore complex regulating chromosome congression (1), became resistant to  (DCV) infection, evidenced in increased survival rates and reduced viral loads, compared to the wild-type control. Mechanistic analysis further showed that Bub1 also functioned in the cytoplasm and was essentially involved in clathrin-dependent endocytosis of DCV and other pathogens, thus limiting pathogen entry. DCV infection potentially had strengthened the interaction between Bub1 and the clathrin adaptor on the cell membrane. Furthermore, the conserved function of Bub1 was also verified in a mammalian cell line. Thus, our data demonstrated a previously unknown function of Bub1 that could be hijacked by pathogens to facilitate their infection and spread. 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  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  in -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.

Shuo Yang

The Joint Center for Infection and Immunity,
Guangzhou Institute of Pediatrics,
The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics

Guangzhou Women and Children's medical center

Establishment of Viral Infection and Analysis of Host-Virus Interaction in Drosophila Melanogaster

Shuo Yang

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}The Joint Center for Infection and Immunity,Guangzhou Institute of Pediatrics,The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics

Guangzhou Women and Children's medical center

Establishment of Viral Infection and Analysis of Host-Virus Interaction in Drosophila Melanogaster

The Joint Center for Infection and Immunity,
Guangzhou Institute of Pediatrics,
The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics