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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.12
- 수록면
- 195 - 207 (13page)
- DOI
- 10.7853/kjvs.2021.44.4.195
이용수
초록· 키워드
오류제보하기
Species A rotaviruses (RVAs) replicate and assemble their immature particles within electron dense compartments known as viroplasms, where lipid droplets (LDs) interact with the viroplasm and facilitate viral replication. Despite the importance of LD formation in the life cycle of RVAs, the up-stream molecules modulating LD formation remain unclear. This study aimed to find out the role of sterol regulatory element-binding proteins (SREBPs) in reprogramming of LD formation after RVA infection. Here, we demonstrate that RVA infection reprograms the sterol regulatory element-binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells, and that both SREBP-1 and -2 transactivated genes, which are involved in fatty acid and cholesterol biosynthesis, are essential for LD formation. Our results showed that pharmacological inhibition of SREBPs using AM580 and betulin and inhibition of their downstream cholesterol biosynthesis (simvastatin for HMG-CoA re-ductase) and fatty acid enzymes (TOFA) negatively modulated the intracellular triacylglycerides and cholesterol levels and their resulting LD and viroplasm formations. Interestingly, pharmacological inhibition of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny production. This study identified SREBPs-mediated lipogenic reprogramming in RVA-infected host cells, which facilitates virus replication through LD formation and its interaction with viroplasms, suggesting that SREBPs can be a potential target for the development of efficient and affordable therapeutics against RVA infection.
목차
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참고문헌 (33)
참고문헌 신청
Ayala-Breton C / 2009 / Analysis of the kinetics of transcription and replication of the rotavirus genome by RNA interference / J Virol 83(17):8819~8831
Carreño-Torres JJ / 2010 / Characterization of viroplasm formation during the early stages of rotavirus infection / Virol J 7:350
Casalino-Matsuda M / 2019 / Hypercapnia increases influenza A virus replication in airway epithelium through a sterolregulatory element binding protein 2 (SREBP2)-dependent mechanism / Am J Respir Crit Care Med 199:A5748
Cheung W / 2010 / Rotaviruses associate with cellular lipid droplet components to replicate in viroplasms, and compounds disrupting or blocking lipid droplets inhibit viroplasm formation and viral replication / J Virol 84:6782~6798
Crawford SE / 2016 / Lipid droplets form complexes with viroplasms and are crucial for rotavirus replication / Curr Opin Virol 19:11~15
Carreño-Torres JJ / 2010 / Characterization of viroplasm formation during the early stages of rotavirus infection / Virol J 7:350
Casalino-Matsuda M / 2019 / Hypercapnia increases influenza A virus replication in airway epithelium through a sterolregulatory element binding protein 2 (SREBP2)-dependent mechanism / Am J Respir Crit Care Med 199:A5748
Cheung W / 2010 / Rotaviruses associate with cellular lipid droplet components to replicate in viroplasms, and compounds disrupting or blocking lipid droplets inhibit viroplasm formation and viral replication / J Virol 84:6782~6798
Crawford SE / 2016 / Lipid droplets form complexes with viroplasms and are crucial for rotavirus replication / Curr Opin Virol 19:11~15
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