Role of apoptosis in Duck Tembusu virus infection of duckling brains in vivo

ABSTRACT Interferon (IFN)-stimulated gene 15 (ISG15) is a ubiquitin-like molecule that conjugates to target proteins via a C-terminal LRLRGG motif and has antiviral function in vivo. We used structural modeling to predict human ISG15 (hISG15) residues important for interacting with its E1 enzyme, UbE1L. Kinetic analysis revealed that mutation of arginine 153 to alanine (R153A) ablated hISG15-hUbE1L binding and transthiolation of UbcH8. Mutation of other predicted UbE1L-interacting residues had minimal effects on the transfer of ISG15 from UbE1L to UbcH8. The capacity of hISG15 R153A to form protein conjugates in 293T cells was markedly diminished. Mutation of the homologous residue in mouse ISG15 (mISG15), arginine 151, to alanine (R151A) also attenuated protein ISGylation following transfection into 293T cells. We assessed the role of ISG15-UbE1L interactions in control of virus infection by constructing double subgenomic Sindbis viruses that expressed the mISG15 R151A mutant. While expression of mISG15 protected alpha/beta-IFN-receptor-deficient (IFN-αβR−/−) mice from lethality following Sindbis virus infection, expression of mISG15 R151A conferred no survival benefit. The R151A mutation also attenuated ISG15's ability to decrease Sindbis virus replication in IFN-αβR−/− mice or prolong survival of ISG15−/− mice. The importance of UbE1L was confirmed by demonstrating that mice lacking this ISG15 E1 enzyme were highly susceptible to Sindbis virus infection. Together, these data support a role for protein conjugation in the antiviral effects of ISG15.

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Response to “A comment on ‘Serological evidence of duck Tembusu virus infection in free‐grazing ducks, Thailand’”

Transboundary and Emerging Diseases ◽

10.1111/tbed.13119 ◽

2019 ◽

Vol 66 (2) ◽

pp. 1098-1099

Author(s):

Wikanda Tunterak ◽

Duangduean Prakairungnamthip ◽

Patchareeporn Ninvilai ◽

Supanat Bunyapisitsopa ◽

Kanisak Oraveerakul ◽

...

Keyword(s):

Virus Infection ◽

Serological Evidence ◽

Duck Tembusu Virus ◽

Free Grazing ◽

Tembusu Virus

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Role of neuromedin B and its receptor in the innate immune responses against influenza A virus infection in vitro and in vivo

Veterinary Research ◽

10.1186/s13567-019-0695-2 ◽

2019 ◽

Vol 50 (1) ◽

Author(s):

Guihong Yang ◽

Huipeng Huang ◽

Mengyao Tang ◽

Zifeng Cai ◽

Cuiqin Huang ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Influenza A ◽

A549 Cells ◽

Virus Challenge ◽

Neuromedin B ◽

Influenza A Virus Infection

Abstract The peptide neuromedin B (NMB) and its receptor (NMBR) represent a system (NMB/NMBR) of neuromodulation. Here, it was demonstrated that the expression of NMBR in cells or murine lung tissues was clearly upregulated in response to H1N1/PR8 influenza A virus infection. Furthermore, the in vitro and in vivo activities of NMB/NMBR during PR8 infection were investigated. It was observed that A549 cells lacking endogenous NMBR were more susceptible to virus infection than control cells, as evidenced by the increased virus production in the cells. Interestingly, a significant decrease in IFN-α and increased IL-6 expression were observed in these cells. The role of this system in innate immunity against PR8 infection was probed by treating mice with NMB. The NMB-treated mice were less susceptible to virus challenge, as evidenced by increased survival, increased body weight, and decreased viral NP expression compared with the control animals. Additionally, the results showed that exogenous NMB not only enhanced IFN-α expression but also appeared to inhibit the expression of NP and IL-6 in PR8-infected cells and animals. As expected, opposing effects were observed in the NMBR antagonist-treated cells and mice, which further confirmed the effects of NMB. Together, these data suggest that NMB/NMBR may be an important component of the host defence against influenza A virus infection. Thus, these proteins may serve as promising candidates for the development of novel antiviral drugs.

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