Molecular biology of canine parainfluenza virus V protein and its potential applications in tumor immunotherapy

Abstract

Canine parainfluenza virus (CPIV) is a zoonotic virus that is widely distributed and is the main pathogen causing canine infectious respiratory disease (CIRD), also known as "kennel cough," in dogs. The CPIV-V protein is the only nonstructural protein of the virus and plays an important role in multiple stages of the virus life cycle by inhibiting apoptosis, altering the host cell cycle and interfering with the interferon response. In addition, studies have shown that the V protein has potential applications in the field of immunotherapy in oncolytic virus therapy or self-amplifying RNA vaccines. In this review, the biosynthesis, structural characteristics and functions of the CPIV-V protein are reviewed with an emphasis on how it facilitates viral immune escape and its potential applications in the field of immunotherapy. Therefore, this review provides a scientific basis for research into the CPIV-V protein and its potential applications.

Keywords: V protein; canine parainfluenza virus; immune escape; molecular mechanism; structure; tumor immunotherapy; viral replication.

Figure 1

Biosynthesis process and structural characteristics of the CPIV-V protein. (A) Genomic characteristics of the V/P gene. U2336 is the conserved editing site in the viral genome. (B) V/P mRNA is produced by different modes of transcription. (C) Sphere model, cartoon representation and C-terminal zinc finger domain of the CPIV-V protein. All protein structures were created on UCSF Chimera. bp, base pairs; aa, amino acid; vRNA, viral RNA; GS, gene start; GE, gene end; NTD, N-terminal domain; CTD, C-terminal domain.

Figure 2

Host antiviral response and multiple antagonistic effects of V protein after CPIV infection. V protein inhibits type I IFN (IFN I) production by antagonizing TRIM25, MDA5, LGP2, TBK1/IKKε, and NFκB and promotes viral replication, budding, and spread by reducing the production of dsRNA, inhibiting tetherin, and binding Rhoa (left). V protein inhibits the IFN response by forming VDC to degrade STAT1 (right).

Figure 3

The expression of saRNA is enhanced by the V protein. (A) Composition of conventional saRNAs and V-protein-encoding saRNAs. (B) V protein antagonizes the innate immune response by inhibiting NF-κB and IFR3 activation, which in turn enhances saRNA expression.

Figure 4

V protein promotes HCV replication and spread. (A) Conventionally, in HCV-Infected HFLC, PAMPs recognize dsRNAs derived from HCV replication, activate the HFLC innate immune response, and inhibit HCV replication and spread. (B) When the V protein is introduced into HFLC by a lentiviral vector, the V protein promotes the replication and spread of HCV by antagonizing IFN-I and IFN-III (IL-29) induced by the HFLC innate immune response.