H T Agostini1, C F Ryschkewitsch, G L Stoner. 1. Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract
OBJECTIVES: The major genotypes of the human polyomavirus JC (JCV) include type 1 (European), type 2 (Asian), type 3 (African), and type 4 (United States). Here we report characterization of the complete genome of a genotype obtained from the brain of an African American with systemic lupus erythematosus (SLE) and progressive multifocal leukoencephalopathy (PML). STUDY DESIGN/ METHODS: DNA extracted from JCV-infected brain tissue was subjected to whole-genome polymerase chain reaction (PCR) amplification and direct cycle sequencing. Relations to other JCV genotypes and the predicted amino acid sequence were analyzed. RESULTS: This African-American type 6 strain (#601) differs from strains of all other genotypes in about 2% of its DNA sequence. The length of the total coding region of strain #601 is increased to 4855 bp by the insertion of a single nucleotide in the large T-antigen intron. This strain, originally placed with the type 2 group on the basis of its sequence in the VT-intergenic region, is very closely related to strains recently identified in the urine of individuals from Ghana, West Africa. CONCLUSIONS: This is the first example of an African JCV genotype identified in the brain of an African-American PML patient. The extent of sequence divergence of JCV type 6 suggests a split of type 6 strains before the separation of types 2 and 3. These findings confirm that distinctive African genotypes of JCV have been maintained in the African-American population and that they are capable of causing PML.
OBJECTIVES: The major genotypes of the humanpolyomavirus JC (JCV) include type 1 (European), type 2 (Asian), type 3 (African), and type 4 (United States). Here we report characterization of the complete genome of a genotype obtained from the brain of an African American with systemic lupus erythematosus (SLE) and progressive multifocal leukoencephalopathy (PML). STUDY DESIGN/ METHODS: DNA extracted from JCV-infected brain tissue was subjected to whole-genome polymerase chain reaction (PCR) amplification and direct cycle sequencing. Relations to other JCV genotypes and the predicted amino acid sequence were analyzed. RESULTS: This African-American type 6 strain (#601) differs from strains of all other genotypes in about 2% of its DNA sequence. The length of the total coding region of strain #601 is increased to 4855 bp by the insertion of a single nucleotide in the large T-antigen intron. This strain, originally placed with the type 2 group on the basis of its sequence in the VT-intergenic region, is very closely related to strains recently identified in the urine of individuals from Ghana, West Africa. CONCLUSIONS: This is the first example of an African JCV genotype identified in the brain of an African-American PML patient. The extent of sequence divergence of JCV type 6 suggests a split of type 6 strains before the separation of types 2 and 3. These findings confirm that distinctive African genotypes of JCV have been maintained in the African-American population and that they are capable of causing PML.
Authors: C L Cubitt; X Cui; H T Agostini; V R Nerurkar; I Scheirich; R Yanagihara; C F Ryschkewitsch; G L Stoner Journal: J Neurovirol Date: 2001-08 Impact factor: 2.643