Abstract
The mitochondrial antiviral signaling (MAVS) protein, a critical adapter, links the upstream recognition of viral RNA to downstream antiviral signal transduction. However, the interaction mechanism between avian metapneumovirus subgroup C (aMPV/C) infection and MAVS remains unclear. Here, we confirmed that aMPV/C infection induced a reduction in MAVS expression in Vero cells in a dose-dependent manner, and active aMPV/C replication was required for MAVS decrease. We also found that the reduction in MAVS occurred at the post-translational level rather than at the transcriptional level. Different inhibitors were used to examine the effect of proteasome or autophagy on the regulation of MAVS. Treatment with a proteasome inhibitor MG132 effectively blocked MAVS degradation. Moreover, we demonstrated that MAVS mainly underwent K48-linked ubiquitination in the presence of MG132 in aMPV/C-infected cells, with amino acids 363, 462, and 501 of MAVS being pivotal sites in the formation of polyubiquitin chains. Finally, E3 ubiquitin ligases for MAVS degradation were screened and identified and RNF5 targeting MAVS at Lysine 363 and 462 was shown to involve in MAVS degradation in aMPV/C-infected Vero cells. Overall, these results reveal the molecular mechanism underlying aMPV/C infection-induced MAVS degradation by the ubiquitin-proteasome pathway.
Highlights
Avian metapneumovirus, previously known as avian pneumovirus (APV), is considered an important pathogen to both turkeys and chickens as it causes respiratory tract disease responsible for economic losses to the poultry industry globally [1,2]. aMPV, a member of the family Paramyxoviridae, has a single-stranded, nonsegmented, negativesense RNA genome [3]
The MTT results showed that the viability of cultured cells was not affected by pharmaceutical reagents (MG132, CQ, and wortmannin) (Figure 2F). These results demonstrate that addition of MG132 largely inhibited mitochondrial antiviral signaling (MAVS) degradation in the aMPV subgroup C (aMPV/C)-infected Vero cells, suggesting that MAVS degradation by aMPV/C is related to the proteasome pathway
To date, no study has investigated whether MAVS expression is regulated by aMPV/C infection and if so, how it is regulated during viral infection
Summary
Avian metapneumovirus (aMPV), previously known as avian pneumovirus (APV), is considered an important pathogen to both turkeys and chickens as it causes respiratory tract disease responsible for economic losses to the poultry industry globally [1,2]. aMPV, a member of the family Paramyxoviridae, has a single-stranded, nonsegmented, negativesense RNA genome [3]. AMPV subgroup C (aMPV/C) infection in turkeys was first reported in the United States in 1999 and subsequently identified in other states of the USA and in France [5,6,7] This virus has been reported and isolated in pheasants in South Korea and in meat-type chickens in China [8,9]. Newcastle disease virus, a member of the Paramyxoviridae family, targets MAVS for ubiquitin-mediated degradation through E3 ubiquitin ligase RING-finger protein 5 (RNF5) [29]. These findings promoted us to investigate the molecular mechanism that exists between aMPV/C infection and MAVS expression. Our results show that the formation of ubiquitin chains occurs at amino acids 363, 462, and 501 of MAVS and RNF5 targeting MAVS at Lysine 363 and 462 is involved in MAVS degradation in the aMPV/Cinfected Vero cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
