Related Experiment Videos
Five complete genomes of JC virus type 3 from Africans and African Americans
H T Agostini1, C F Ryschkewitsch, G R Brubaker
1Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA.
Abstract:
The central demyelinating disease progressive multifocal leukoencephalopathy (PML) is caused by the human polyomavirus JC virus (JCV). JCV evolved as geographically based genotypes of which Type 3 is an African variant first characterized in HIV-1 positive patients from Tanzania. This study reports the complete sequence of five JCV Type 3 strains. The entire JCV genome was PCR amplified from urine specimens of three African and two African-American individuals. The African consensus sequence was compared to the Type 1 and Type 2 prototype strains, JCV (Mad-1) and JCV(GS/B), respectively. Type 3 differed in 2.2% of its coding region genome from JCV (Mad-1) and in 1.3% from JCV(GS/B). Within the coding region the sequence variation among the three types was higher in the capsid protein VP1 and in the regulatory protein large T antigen than in the agnoprotein or in VP2/3. Notable Type 3-specific changes were located at sites adjacent to the zinc finger motif and near the major donor and acceptor splice junctions of large T antigen. Four of the five urinary Type 3 strains had an unrearranged, archetypal regulatory region. African strain #309 showed a 10-bp deletion at a location similar to that previously described for #307 from Tanzania. The African-American Type 3 strain #312 was closely related to the African consensus sequence. The complete genome of a urinary JCV strain from another African-American male, previously reported as a possible Type 5, showed a sequence difference of only 0.52% from the Tanzanian consensus and has been reclassified as a subtype of Type 3.
Insights
This study sequenced five human polyomavirus JC virus (JCV) Type 3 strains, an African variant. Findings reveal genetic variations, particularly in VP1 and large T antigen genes, aiding in classifying new subtypes.
Area of Science:
- Virology
- Genetics
- Neuroscience
Background:
- Progressive multifocal leukoencephalopathy (PML) is a central nervous system demyelinating disease caused by the JC virus (JCV).
- JCV exhibits geographically distinct genotypes, with Type 3 identified as an African variant, initially found in HIV-1 positive individuals in Tanzania.
Purpose of the Study:
- To report the complete genome sequence of five JCV Type 3 strains.
- To analyze the genetic variations within the JCV Type 3 genome and compare it with other JCV types.
Main Methods:
- Polymerase chain reaction (PCR) was used to amplify the entire JCV genome from urine specimens of three African and two African-American individuals.
- Sequencing of the amplified JCV genomes.
- Comparative sequence analysis of Type 3 strains against Type 1 (JCV Mad-1) and Type 2 (JCV GS/B) prototype strains.
Main Results:
- The complete genome sequences of five JCV Type 3 strains were determined.
- Type 3 exhibited a 2.2% coding region difference from JCV (Mad-1) and 1.3% from JCV(GS/B).
- Sequence variations were more pronounced in the VP1 capsid protein and large T antigen genes. Notably, Type 3 strains showed specific changes near the zinc finger motif and splice junctions of the large T antigen. Four strains possessed an archetypal regulatory region, with one African strain showing a 10-bp deletion. An African-American strain previously classified as Type 5 was reclassified as a Type 3 subtype due to high sequence similarity (0.52% difference) to the Tanzanian consensus.
Conclusions:
- The study provides complete genome sequences for JCV Type 3 strains, expanding our understanding of JCV genetic diversity.
- Genetic analysis highlights specific variations in Type 3, particularly in key viral proteins, which may influence viral behavior or pathogenesis.
- Reclassification of a previously identified strain as a Type 3 subtype underscores the genetic relatedness within this JCV variant and its presence in African-American populations.