Comparative analysis of capsid proteins from plant viral nanoparticles: implications for therapeutic potential in cancer immunotherapy

In situ vaccination for cancer immunotherapy uses intratumoral administration of small molecules, proteins, nanoparticles, or viruses that activate pathogen recognition receptors (PRRs) to reprogram the tumor microenvironment and prime systemic antitumor immunity. Cowpea Severe Mosaic Virus (CPSMV) is one of the isometric plant viruses belonging to the order Picornavirales, the family Secoviridae and the genus Comoviridae that naturally infects Cowpea (Vigna unguiculata L.) and is commonly found in Brazil. The most studied member of this family is Cowpea Mosaic Virus (CPMV), which, although not infectious to mammals, activates mammalian PRRs. Application of CPMV as an in situ vaccine results in potent and durable efficacy in tumor-bearing mouse models as well as in canine models. In this work, we performed homology analysis between the CPMV coat proteins and a CPSMV isolate from the Northeast Region of Brazil. The complete genomic sequence of the Brazilian CPSMV isolate (MW392574.1), obtained from cowpea plants, was compared with a CPMV sequence (NC_003550.1), both deposited in GenBank, using the BLAST algorithm. Amino acid sequences were aligned and pairwise comparisons between capsid protein sequences were performed. The general organization of the CPSMV genome follows that of the CPMV genome, with both viruses having a bipartite positive-sense RNA genome. RNA-1 encodes proteins involved in replication, while RNA-2 encodes structural proteins. Regarding capsid proteins, both CPMV and CPSMV have capsids with pseudo-T symmetry (pT = 3) composed of proteins S (small) and L (large), which are repeated 60 times to form the capsid. Homology analysis revealed that there is significant similarity between the capsid proteins of the two viruses. Specifically, the S proteins of CPMV (180 aa) and CPSMV (181 aa) present 37.22% of identities, while the L proteins of CPMV (369 aa) and CPSMV (366 aa) present 48.09% of identities. These data indicate that, although the two viruses are distinct, they are strongly related. Given the therapeutic potential already demonstrated by CPMV, CPSMV may also have therapeutic potential against cancer, justifying further investigation into its use in immunotherapy.

Corresponding author: Renata Kelly de Freitas Mano (e-mail: renata.mano@aluno.uece.br).