Selective SLAM/CD150 receptor-detargeting of canine distemper virus

Gradauskaite, Vaiva; Khosravi, Mojtaba; Plattet, Philippe

doi:10.1016/j.virusres.2022.198841

Cited by 4 publications

(4 citation statements)

References 41 publications

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“…To control the specificity of the SLAM binding activity in this experiment, we included a soluble protein carrying a point mutation that is known to disrupt the SLAM interaction (solHwt R529A -TST) ( Fig. 4A , right panel) ( 10 , 43 , 44 ).…”

Section: Resultsmentioning

confidence: 99%

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LRP6 Is a Functional Receptor for Attenuated Canine Distemper Virus

Gradauskaite

Inglebert

Doench

et al. 2023

mBio

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Section: Resultsmentioning

confidence: 99%

“…Soluble proteins. A dimeric form of soluble Hwt (solH-TST) as well as soluble V-domain canine SLAM (solSLAM.V-Fc) were previously described (43). The gene encoding a soluble form of the canine LRP6 protein (UniProt: A0A8C0NS55_CANLF: aa 20 to 1,246) fused to a human Fc domain (solLRP6-Fc) was synthesized at Twist Bioscience.…”

Section: Methodsmentioning

confidence: 99%

LRP6 Is a Functional Receptor for Attenuated Canine Distemper Virus

Gradauskaite

Inglebert

Doench

et al. 2023

mBio

Self Cite

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“…There is consistency with the pathogenesis for each animal species for which the clinical disease has been described [ 32 ]. Binding of the virus to SLAM provides viral tropism for immune cells and causes viremia and immunosuppression, while binding to nectin-4 provides tropism for epithelial cells and is crucial for the development of clinical signs, cell-to-cell spread, and exit from cells, which results in virus shedding [ 1 , 2 , 12 , 46 ]. Nectin-4 has also been suggested to play a role in the neurotropism of CDV; however, other, thus far uncharacterized, receptors might be involved in infection of astrocytes [ 1 , 12 , 47 ].…”

Section: Virus Tropism and Pathogenesismentioning

confidence: 99%

Canine Distemper Virus in Endangered Species: Species Jump, Clinical Variations, and Vaccination

Wilkes

2022

Pathogens

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Canine morbillivirus (Canine distemper virus, CDV) is the cause of distemper in a large number of different species, some of which are endangered. The clinical outcome associated with infection is variable and based on many factors, including the host species, the immune response of the individual animal to the infection, and variation in virus tropism and virulence. Unfortunately, the viral characteristics associated with virulence versus attenuation are not fully characterized, nor are the specific mutations that allow this virus to easily move and adapt from one species to another. Due to its wide host range, this virus is difficult to manage in ecosystems that are home to endangered species. Vaccination of the domestic dog, historically considered the reservoir species for this virus, at dog-wildlife interfaces has failed to control virus spread. CDV appears to be maintained by a metareservoir rather than a single species, requiring the need to vaccinate the wildlife species at risk. This is controversial, and there is a lack of a safe, effective vaccine for nondomestic species. This review focuses on topics that are paramount to protecting endangered species from a stochastic event, such as a CDV outbreak, that could lead to extinction.

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“…Finally, the virus invades the central nervous system (CNS), inducing severe neurological disease by establishing persistent infection (16). Considering the important role of SLAM and Nectin-4 in the host recognition of CDV, pathogenicity, and virus transmission (20), SLAM and Nectin-4 receptor may be targets for development of antiviral agents to block CDV infection.…”

Section: Introductionmentioning

confidence: 99%

Development of HEK293T-produced recombinant receptor-Fc proteins as potential candidates against canine distemper virus

Song

Huang

2023

Front. Vet. Sci.

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Canine distemper (CD) is a highly contagious viral disease worldwide. Although live attenuated vaccine is available as a preventive measure against the disease, cases of vaccination failure highlight the importance of potential alternative agent against canine distemper virus (CDV). CDV infects cells mainly by binding signaling lymphocyte activation molecule (SLAM) and Nectin-4 receptor. Here, to develop a new and safe antiviral biological agent for CD, we constructed and expressed CDV receptor proteins fused with Fc region of canine IgG-B, namely, SLAM-Fc, Nectin-Fc and SLAM-Nectin-Fc in HEK293T cells, and antiviral activity of these receptor-Fc proteins was subsequently evaluated. The results showed that the receptor-Fc proteins efficiently bound to receptor binding domain (RBD) of CDV-H, meanwhile, these receptor-Fc proteins competitively inhibited the binding of His-tagged receptor proteins (SLAM-His or Nectin-His) to CDV-H-RBD-Flag protein. Importantly, receptor-Fc proteins exhibited potent anti-CDV activity in vitro. Treatment with receptor-Fc proteins at the pre-entry stage dramatically suppressed CDV infectivity in Vero cells stably expressing canine SLAM. The minimum effective concentration (MEC) of SLAM-Fc, Nectin-Fc and SLAM-Nectin-Fc was 0.2 μg/mL, 0.2 μg/mL, 0.02 μg/mL. The 50% inhibition concentration (IC50) of three proteins was 0.58 μg/mL, 0.32 μg/mL and 0.18 μg/mL, respectively. Moreover, treatment with receptor-Fc proteins post viral infection can also inhibit CDV reproduction, the MEC of SLAM-Fc, Nectin-Fc and SLAM-Nectin-Fc was same as pre-treatment, and the IC50 of receptor-Fc proteins was 1.10 μg/mL, 0.99 μg/mL and 0.32 μg/mL, respectively. The results suggested that the receptor-Fc proteins were more effective for pre-entry treatment than post-infection treatment, furthermore, SLAM-Nectin-Fc was more effective than SLAM-Fc and Nectin-Fc. These findings revealed the receptor-Fc proteins were promising candidates as inhibitor against CDV.

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Selective SLAM/CD150 receptor-detargeting of canine distemper virus

Cited by 4 publications

References 41 publications

LRP6 Is a Functional Receptor for Attenuated Canine Distemper Virus

LRP6 Is a Functional Receptor for Attenuated Canine Distemper Virus

Canine Distemper Virus in Endangered Species: Species Jump, Clinical Variations, and Vaccination

Development of HEK293T-produced recombinant receptor-Fc proteins as potential candidates against canine distemper virus

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