Nucleotide sequence analysis of a provirus derived from an individual with tropical spastic paraparesis.
Human T-cell lymphotropic virus type 1 (HTLV-1), the cause of inapparent infections and T-cell leukemias and lymphomas, has also been implicated in two chronic neurological diseases, tropical spastic paraparesis (TSP) and HTLV-1 associated myelopathy (HAM). We initiated a search for a neurotropic variant of HTLV-1 that might be responsible for these chronic progressive myelopathies by cloning and sequencing a provirus from a T-cell line from an individual with TSP. The LTRs and genes of the TSP provirus differ from HTLV-1 by 20-30 nucleotides in each region, but none of the substitutions ostensibly affect functional sites with the exception of the env gene. We document one substitution in the region encoding gp46 common to TSP and HAM proviruses and a mutation that introduces two stop codons in the region encoding gp21. The latter should delete about 100 amino acids from the transmembrane anchor, and, for this reason, the progeny of the sequenced provirus are likely to be defective viruses, maintained in the culture through coinfection of cells with wild-type non-defective HTLV-1. While defective viruses could be responsible for persistent infection of the nervous system in TSP, this cannot be generally the case as we show that HTLV-1 DNA amplified from cell lines from two other individuals with TSP lacked the stop codons. Similarly, comparisons of DNA amplified from HTLV-1 DNA in cases of ATL, HAM, and TSP did not establish a correlation between the mutation in gp46 and neurological disease. The issue of neurotropic variants in HTLV-1 associated neurological disease thus remains an open one which may be resolved in the future by examining proviruses in cells in the lesions in the nervous system; or proviruses in ATL and HAM/TSP which differ in their ability to replicate in glial or neuronal cells.
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455.
A
A
Evangelista
S
S
Maroushek
H
H
Minnigan
A
A
Larson
E
E
Retzel
A
A
Haase
D
D
Gonzalez-Dunia
D
D
McFarlin
E
E
Mingioli
S
S
Jacobson
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000235:genetics; D015686:Gene Products, env / Q000235:genetics; D015752:Genes, env; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015493:Paraparesis, Tropical Spastic / Q000382:microbiology*; D011533:Proviruses / Q000235:genetics*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D004279:DNA, Viral; D015686:Gene Products, env