M1 virus mutant and use thereof

An M1 virus, wherein an amino acid residue corresponding to the 358th site of the NS3 protein encoded by a nucleotide sequence of the M1 virus is not M;

• and/or an amino acid residue corresponding to the 4th site of the E2 protein is not E or K;
• preferably, the nucleotide sequence of the M1 virus has at least 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% or at least 99.5% or at least 99.8% or at least 99.9% or 100% sequence identity with an M1 sequence shown as SEQ ID NO:
• 5 or SEQ ID NO:
• 15 or GenBank Accession No. EU015061.1 or GenBank Accession No. EF011023.1 or CCTCC V201423;
• preferably, the amino acid residue corresponding to the 358th site of the NS3 protein is:
• G, A, L, I, V, P, S, Q, T, C, N, F, Y, W, D, E, K, R or H;
• and/or the amino acid residue corresponding to the 4th site of the E2 protein is:
• M, G, A, L, I, V, P, S, Q, T, C, N, F, Y, W, D, R or H;
• preferably, the M1 virus has a mutation of the amino acid site relative to a wild-type M1 virus or a pseudo-wild-type M1 virus;
• preferably, the M1 virus has a mutation of the amino acid site relative to an M1 virus having a sequence shown as SEQ ID NO:
• 5 or an M1 virus having a sequence shown as SEQ ID NO:
• 15;
• preferably, the mutation is:
• M358G, M358A, M358L, M358I, M358V, M358P, M358S, M358Q, M358T, M358C, M358N, M358F, M358Y, M358W, M358D, M358E, M358K, M358R or M358H on the NS3 protein;
• and/or K4M, K4G, K4A, K4L, K4I, K4V, K4P, K4S, K4Q, K4T, K4C, K4N, K4F, K4Y, K4W, K4D, K4R, K4H, E4M, E4G, E4A, E4L, E4I, E4V, E4P, E4S, E4Q, E4T, E4C, E4N, E4F, E4Y, E4W, E4D, E4R or E4H on the E2 protein;
• preferably, the M1 virus is obtained by a mutation of an amino acid residue M corresponding to the 358th site of the NS3 protein of the M1 virus having the sequence shown as SEQ ID NO:
• 5 into:
• G, A, L, I, V, P, S, Q, T, C, N, F, Y, W, D, E, K, R or H;
• and/or a mutation of an amino acid residue K at the 4th site of the E2 protein into:
• M, G, A, L, I, V, P, S, Q, T, C, N, F, Y, W, D, R or H;
• and
• preferably, the amino acid residue M corresponding to the 358th site of the NS3 protein of the M1 virus mutates into L relative to the M1 virus having the sequence shown as SEQ ID NO:
• 15;
• and/or the amino acid residue E corresponding to the 4th site of the E2 protein mutates into D.

A vector, comprising a nucleic acid for encoding the E2 protein of an M1 virus, and/or the NS3 protein, wherein an amino acid residue corresponding to the 358th site of the NS3 protein is not M;

• and an amino acid residue corresponding to the 4th site of the E2 protein is not E or K;
• preferably, the amino acid residue corresponding to the 358th site of the NS3 protein is:
• G, A, L, I, V, P, S, Q, T, C, N, F, Y, W, D, E, K, R or H;
• preferably, the amino acid residue corresponding to the 4th site of the E2 protein is:
• M, G, A, L, I, V, P, S, Q, T, C, N, F, Y, W, D, R or H;
• preferably, an amino acid sequence of the NS3 protein has at least 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% or at least 99.5% or at least 99.8% or at least 99.9% or 100% sequence identity with an amino acid sequence shown as SEQ ID NO:
• 8 or SEQ ID NO:
• 18;
• preferably, an amino acid sequence of the E2 protein has at least 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% or at least 99.5% or at least 99.8% or at least 99.9% or 100% sequence identity with an amino acid sequence shown as SEQ ID NO:
• 12 or SEQ ID NO:
• 31;
• preferably, the vector further comprises a coding sequence of the NS1 protein, the NS2 protein, the NS4 protein, the C protein, the E3 protein, the 6K protein, and/or the E1 protein of the M1 virus;
• preferably, an amino acid sequence of the NS1 protein has at least 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% or at least 99.5% or at least 99.8% or at least 99.9% or 100% sequence identity with an amino acid sequence shown as SEQ ID NO:
• 6 or SEQ ID NO:
• 16;
• preferably, an amino acid sequence of the NS2 protein has at least 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% or at least 99.5% or at least 99.8% or at least 99.9% or 100% sequence identity with an amino acid sequence shown as SEQ ID NO:
• 7 or SEQ ID NO:
• 17;
• preferably, an amino acid sequence of the NS4 protein has at least 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% or at least 99.5% or at least 99.8% or at least 99.9% or 100% sequence identity with an amino acid sequence shown as SEQ ID NO:
• 9 or SEQ ID NO:
• 19;
• preferably, an amino acid sequence of the C protein has at least 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% or at least 99.5% or at least 99.8% or at least 99.9% or 100% sequence identity with an amino acid sequence shown as SEQ ID NO:
• 10 or SEQ ID NO:
• 20;
• preferably, an amino acid sequence of the E3 protein has at least 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% or at least 99.5% or at least 99.8% or at least 99.9% or 100% sequence identity with an amino acid sequence shown as SEQ ID NO:
• 11 or SEQ ID NO:
• 30;
• preferably, an amino acid sequence of the 6K protein has at least 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% or at least 99.5% or at least 99.8% or at least 99.9% or 100% sequence identity with an amino acid sequence shown as SEQ ID NO:
• 13 or SEQ ID NO:
• 32;
• preferably, an amino acid sequence of the E1 protein has at least 90% or at least 91% or at least 92% or at least 93% or at least 94% or at least 95% or at least 96% or at least 97% or at least 98% or at least 99% or at least 99.5% or at least 99.8% or at least 99.9% or 100% sequence identity with an amino acid sequence shown as SEQ ID NO:
• 14 or SEQ ID NO:
• 33;
• preferably, the vector further comprises exogenous genes relative to the M1 virus;
• preferably, the exogenous genes express anti-tumor-associated molecules;
• preferably, the vector is selected from viruses;
• preferably, the vector is selected from a retrovirus, a Newcastle disease virus, a rabies virus, a vesicular stomatitis virus, a Maraba virus, an alphavirus, a Newcastle disease virus, a reovirus, an adenovirus, an adeno-associated virus, a herpes simplex virus, a vaccinia virus, or a measles virus;
• and
• preferably, the vector is selected from plasmids.