Primate T-lymphotropic viruses
Disclosed are compositions and methods related to the isolation and identification of the primate T-lymphotropic viruses, HTLV-3 and HTLV-4. The diversity of HTLVs was investigated among central Africans reporting contact with NHP blood and body fluids through hunting, butchering, and keeping primate pets. Herein it is shown that this population is infected with a variety of HTLVs, including two retroviruses; HTLV-4 is the first member of a novel phylogenetic lineage that is distinct from all known HTLVs and STLVs; HTLV-3 falls within the genetic diversity of STLV-3, a group that has not previously been seen in humans. The present disclosure also relates to vectors and vaccines for use in humans against infection and disease. The disclosure further relates to a variety of bioassays and kits for the detection and diagnosis of infection with and diseases caused by HTLV-3 and HTLV-4 and related viruses.
1. An isolated primate T-lymphotropic virus (PTLV) polypeptide, wherein the polypeptide is a HTLV-3 or HTLV-4 gag, pol, env, tax, rex or pro protein selected from the group consisting of:
(i) a HTLV-3 gag protein encoded by a nucleic acid sequence at least 91.5% identical to SEQ ID NO: 35;
(ii) a HTLV-3 pol protein encoded by a nucleic acid sequence at least 92.8% identical to SEQ ID NO: 1;
(iii) a HTLV-3 env protein encoded by a nucleic acid sequence at least 92.5% identical to SEQ ID NO: 3;
(iv) a HTLV-3 tax protein encoded by a nucleic acid sequence at least 94.2% identical to SEQ ID NO: 5;
(v) a HTLV-3 rex protein encoded by a nucleic acid sequence comprising SEQ ID NO: 49;
(vi) a HTLV-3 pro protein encoded by a nucleic acid sequence comprising SEQ ID NO: 47;
(vii) a HTLV-4 gag protein encoded by a nucleic acid sequence comprising nucleotides 750-2024 of SEQ ID NO: 81;
(viii) a HTLV-4 pol protein encoded by a nucleic acid sequence at least 71.5% identical to SEQ ID NO: 2;
(ix) a HTLV-4 env protein encoded by a nucleic acid sequence at least 73.5% identical to SEQ ID NO: 4;
(x) a HTLV-4 tax protein encoded by a nucleic acid sequence at least 82% identical to SEQ ID NO: 6;
(xi) a HTLV-4 rex protein encoded by a nucleic acid sequence comprising SEQ ID NO: 61; and
(xii) a HTLV-4 pro protein encoded by a nucleic acid sequence comprising SEQ ID NO: 59.
2. The isolated PTLV polypeptide of claim 1 , wherein the protein is encoded by a nucleic acid sequence comprising SEQ ID NO: 35; SEQ ID NO: 1; SEQ ID NO: 3; SEQ ID NO: 5; SEQ ID NO: 49; SEQ ID NO: 47; nucleotides 750-2024 of SEQ ID NO: 81; SEQ ID NO: 2; SEQ ID NO: 4; SEQ ID NO: 6; SEQ ID NO: 61 or SEQ ID NO: 59.
3. The isolated PTLV polypeptide of claim 1 , wherein the protein comprises:
(i) an amino acid sequence having at least 95% homology to the amino acid sequence set forth as SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 37, SEQ ID NO: 50, SEQ ID NO: 48, SEQ ID NO: 46, SEQ ID NO: 57, SEQ ID NO: 54, SEQ ID NO: 62, SEQ ID NO: 60, or SEQ ID NO: 58;
(ii) a conservative substitution of 1 or 2 amino acids of the amino acid sequence set forth as one of SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 37, SEQ ID NO: 50, SEQ ID NO: 48, SEQ ID NO: 46, SEQ ID NO: 57, SEQ ID NO: 54, SEQ ID NO: 62, SEQ ID NO: 60, or SEQ ID NO: 58; or
(iii) a deletion of 2 to 6 amino acids of the amino acid sequence set forth as one of SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 37, SEQ ID NO: 50, SEQ ID NO: 48, SEQ ID NO: 46, SEQ ID NO: 57, SEQ ID NO: 54, SEQ ID NO: 62, SEQ ID NO: 60, or SEQ ID NO: 58.
4. The isolated PTLV polypeptide of claim 1 , wherein the amino acid sequence of the protein comprises SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 37, SEQ ID NO: 50, SEQ ID NO: 48, SEQ ID NO: 46, SEQ ID NO: 57, SEQ ID NO: 54, SEQ ID NO: 62, SEQ ID NO: 60, or SEQ ID NO: 58.
5. The isolated PTLV polypeptide of claim 1 , wherein the amino acid sequence of the protein consists of SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 37, SEQ ID NO: 50, SEQ ID NO: 48, SEQ ID NO: 46, SEQ ID NO: 57, SEQ ID NO: 54, SEQ ID NO: 62, SEQ ID NO: 60, or SEQ ID NO: 58.
6. A method for detecting antibodies to a PTLV in a biological sample, comprising contacting the biological sample with the polypeptide of claim 1 , wherein binding of antibodies from the biological sample to the polypeptide indicates the presence of antibodies to the PTLV in the biological sample.
7. The method of claim 6 , wherein the PTLV is HTLV-3 or HTLV-4.
8. The method of claim 6 , wherein the biological sample comprises a body fluid sample.
9. A kit for detecting the presence of antibodies that bind a PTLV in a sample, wherein the kit comprises at least one polypeptide of claim 1 .
10. The kit of claim 9 , wherein the PTLV is HTLV-3 or HTLV-4.
11. The method of claim 6 , wherein the protein is encoded by a nucleic acid sequence comprising SEQ ID NO: 35; SEQ ID NO: 1; SEQ ID NO: 3; SEQ ID NO: 5; SEQ ID NO: 49; SEQ ID NO: 47; nucleotides 750-2024 of SEQ ID NO: 81; SEQ ID NO: 2; SEQ ID NO: 4; SEQ ID NO: 6; SEQ ID NO: 61 or SEQ ID NO: 59.
12. The method of claim 6 , wherein the protein comprises:
(i) an amino acid sequence having at least 95% homology to the amino acid sequence set forth as SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 37, SEQ ID NO: 50, SEQ ID NO: 48, SEQ ID NO: 46, SEQ ID NO: 57, SEQ ID NO: 54, SEQ ID NO: 62, SEQ ID NO: 60, or SEQ ID NO: 58;
(ii) a conservative substitution of 1 or 2 amino acids of the amino acid sequence set forth as one of SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 37, SEQ ID NO: 50, SEQ ID NO: 48, SEQ ID NO: 46, SEQ ID NO: 57, SEQ ID NO: 54, SEQ ID NO: 62, SEQ ID NO: 60, or SEQ ID NO: 58; or
(iii) a deletion of 2 to 6 amino acids of the amino acid sequence set forth as one of SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 37, SEQ ID NO: 50, SEQ ID NO: 48, SEQ ID NO: 46, SEQ ID NO: 57, SEQ ID NO: 54, SEQ ID NO: 62, SEQ ID NO: 60, or SEQ ID NO: 58.
13. The method of claim 6 , wherein the amino acid sequence of the protein comprises SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 37, SEQ ID NO: 50, SEQ ID NO: 48, SEQ ID NO: 46, SEQ ID NO: 57, SEQ ID NO: 54, SEQ ID NO: 62, SEQ ID NO: 60, or SEQ ID NO: 58.
14. The method of claim 6 , wherein the amino acid sequence of the protein consists of SEQ ID NO: 40, SEQ ID NO: 44, SEQ ID NO: 37, SEQ ID NO: 50, SEQ ID NO: 48, SEQ ID NO: 46, SEQ ID NO: 57, SEQ ID NO: 54, SEQ ID NO: 62, SEQ ID NO: 60, or SEQ ID NO: 58.