Background
Infection with canine distemper virus (CDV), a highly infectious agent that causes canine distemper characterized by fever, pneumonia, severe manifestations of leukopenia, and neurological deficits, has led to severe and often fatal disease in a large number of carnivores. CDV is an enveloped single-stranded negative-sense RNA virus whose genome contains 15,690 nucleotides encoding six structural and two nonstructural proteins. The structural proteins include nucleocapsid protein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), hemagglutinin protein (H), and large protein (L). L proteins are associated with N and P proteins, P proteins are cofactors for RNA polymerase, H proteins mediate viral binding to the cell membrane, and F proteins perform viral fusion with the cell membrane and facilitate entry of the viral genome into the cytoplasm. Nonstructural proteins, including V and C proteins, are associated with host immunosuppression. V proteins inhibit nuclear translocation of STAT1 and STAT2, thereby interfering with type I and type II interferon (IFN)-mediated transcriptional activation and antagonizing innate immunity. C proteins are involved in lymphoid organ transmission of CDV.
The signaling lymphocyte activation molecule (SLAM or CD150), expressed on activated T cells, immature thymocytes, memory T cells, B cells, activated monocytes, and dendritic cells, and the adhesion junction protein, nectin-4, preferentially expressed in tracheobronchial epithelial cells, are lymphocyte and epithelial cell receptors, respectively, that recognize CDV. The virus first enters the respiratory tract, interacts with SLAM-positive immune cells, and then migrates through infected cells to local draining lymph nodes, where the virus spreads to T and B cells. Infected circulating immune cells then spread the virus throughout the lymphatic system, followed by infiltration of the lamina propria by myeloid cells and spread of the virus to epithelial tissues by contact with nectin-4. Finally, the virus invades the central nervous system and induces severe neurologic disease by establishing a persistent infection.
Figure 1. Diagram illustrating two CDV entry pathways into the CNS
(Source: Zhao J, et al. 2022)
Alternative Names
Native canine distemper virus Antigen
References
- 1. Zhao J, et al. Multiple Receptors Involved in Invasion and Neuropathogenicity of Canine Distemper Virus: A Review. Viruses. 2022 Jul 12;14(7):1520.
- 2. Wilkes RP. Canine Distemper Virus in Endangered Species: Species Jump, Clinical Variations, and Vaccination. Pathogens. 2022 Dec 29;12(1):57.
References
A method for screening CDV microneutralization activity in microvolume samples
J Virol Methods
Authors: Deng X, Su J, Hu B, Bai X.
Abstract
Objective: This study aims to establish a screening method for canine distemper virus (CDV) microneutralizing activity suitable for microvolume samples.
Methods: This method is based on the Indirect immunofluorescence assay (IFA) established on Vero-slam cells. First, by comparing the sensitivities of CDV neutralizing monoclonal antibody (1C42H11) and NP protein monoclonal antibody (CDV-NP) in IFA experiments, CDV-NP was selected as the primary antibody. Then, by detecting the infection rates of multi-concentrations of CDV neutralized with water, the minimum CDV concentration with an infection rate greater than 90% was defined as the minimum stable infection concentration, which was used as the neutralizing solution for this method. Finally, the CDV-positive neutralizing serum (neutralizing titer 1:708) was diluted into multiple dilution groups as test samples, and then neutralized in equal volumes with the neutralizing solution to detect the neutralizing activity detection rates of each dilution group and the lowest detection limit of this method.
Results: The results showed that the neutralizing activity of serum with a CDV neutralizing titer of 1:708 diluted 212 times was the lowest limit of detection, and the detection rate of microneutralizing activity was 63.54 ± 4.774%.
Conclusion: This study established an economical, stable, and easy-to-operate CDV microneutralizing activity high-throughput screening method, laying a methodological foundation for the development of native CDV neutralizing antibodies based on single B cells.
Canine distemper virus (CDV)-neutralizing activities of an anti-CDV canine-derived single-chain variable antibody fragment 4-15 (scFv 4-15) screened by phage display technology
Int J Biol Macromol
Authors: Li Y, Song J, Jiang S, Yang Y, Han Y, Zhong L, Zhou J, Wang M, Song H, Xu Y.
Abstract
Canine distemper virus (CDV) is a highly contagious pathogen that causes severe diarrhea, fever and vomiting in domestic dogs, posing a serious threat to the dog breeding industry. Currently, there are no effective therapeutic agents for emergency treatment despite the availability of vaccines against CDV infection. Single-chain fragment variable (scFv) antibody has been demonstrated to effectively inhibit virus infections, suggesting a potential candidate as a therapeutic agent for canine distemper. In this study, a phage-displayed scFv library was constructed from the peripheral blood lymphocytes of dog immunized intramuscularly with live-attenuated CDV vaccine, and was subjected to four rounds of pannings against CDV. Subsequent indirect enzyme-linked immunosorbent assay screening revealed high-affinity scFv antibodies specific to CDV, and indirect immunofluorescence assay screening revealed CDV-neutralizing activity of scFv antibodies. Our results showed that a scFv antibody 4-15 (scFv 4-15) with high-affinity binding to CDV and neutralizing activity against CDV was obtained, which displayed effective therapeutic potential in vivo for dogs challenged with a lethal dose of CDV. Conclusively, the scFv 4-15 with high-affinity binding and neutralizing activity to CDV that was obtained by phage display technology provides a promising candidate for the therapeutic agents against CDV infection.
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