Flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), rely heavily on the availability of endoplasmic reticulum (ER) membranes throughout their lifecycle and degradation of ER membranes restricts flavivirus replication. Accordingly, DENV and ZIKV restrict ER turnover by protease-mediated cleavage of reticulophagy regulator 1 (RETREG1), also known as FAM134B, an autophagy receptor responsible for targeted ER sheet degradation. Given that the induction of autophagy may play an important role in flavivirus replication, the antiviral role of RETREG1 suggests specialized autophagic pathways may have differential effects on the flavivirus lifecycle. We previously identified BPI Fold Containing Family B Member 3 (BPIFB3) as a regulator of autophagy that negatively controls enterovirus replication. Here, we show that in contrast to enteroviruses, BPIFB3 functions as a positive regulator of DENV and ZIKV infection and that its RNAi-mediated silencing inhibits the formation of viral replication organelles. Mechanistically, we show that depletion of BPIFB3 enhances RETREG1-dependent reticulophagy leading to enhanced ER turnover and the suppression of viral replication. Consistent with this, the antiviral effects of BPIFB3 depletion can be reversed by RETREG1 silencing, suggesting a specific role for BPIFB3 in regulating ER turnover. These studies define BPIFB3 as a required host factor for both DENV and ZIKV replication and further contribute to our understanding of the requirements for autophagy during flavivirus infection.Flaviviruses and other arthropod transmitted viruses represent a widespread global health problem with limited treatment options currently available. Thus, a better understanding of the cellular requirements for their infection is needed. Both DENV and ZIKV rely on expansion of the endoplasmic reticulum (ER) and the induction of autophagy to establish productive infections. However, little is known regarding the interplay between the requirements for autophagy initiation during infection and the mechanisms used by these viruses to avoid clearance through the autophagic pathway. Our study highlights the importance of the host factor BPIFB3 in regulating flavivirus replication and further confirms that the RETREG1-dependent reticulophagy pathway is antiviral to both DENV and ZIKV.Copyright © 2020 American Society for Microbiology.
January 23, 2020
Intergenerational transmission of chronic pain-related disability: the explanatory effects of depressive symptoms.
September 7, 2020
More than just a common cold: Endemic coronaviruses OC43, HKU1, NL63, and 229E associated with severe acute respiratory infection and fatality cases among healthy adults.
July 30, 2020
- ACC 2020The American College of Cardiology decided to cancel ACC.20/WCC due to COVID-19, which was scheduled to take place March 28-30 in Chicago. However, ACC.20/WCC Virtual Meeting continues to release cutting edge science and practice changing updates for cardiovascular professionals on demand and free through June 2020.
- CROI 2020Every year, CROI hosts some of the world's leading experts in HIV research, who come to present exciting new data and drive forward the field of HIV/AIDS research. This year, due to COVID-19, CROI held their meeting virtually.