Virus Evolution Workgroup: 1999 Workshop Abstract
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JC virus in the South Pacific: New variants with an unusual regulatory region rearrangement in the Papua New Guinea Highlands
Gerald L. Stoner1, Jonathan S. Friedlaender2, David
V. Jobes1, Hansjurgen T. Agostini1, Sylvester C. Chima1,
Charles S. Mgone3, Richard Yanagihara4 and Caroline F.
Ryschkewitsch1
1National Institute of Neurological Disorders and Stroke,
National Institutes of Health, Bethesda, MD; 2Department of Anthropology,
Temple University, Philadelphia, PA; 3Institute of Medical Research,
Goroka, Papua New Guinea; 4Retrovirology Research Laboratory, Pacific
Biomedical Research Center, University of Hawaii at Manoa, HI
JC virus (JCV), a human polyomavirus, establishes a persistent infection in the kidney from which the virus is excreted by 20-70% of the population in all parts of the world. The circular 5.1-kb genome consists of a regulatory region between early (T antigens) and late (capsid proteins, VP1-3) transcription units. A portion of the VP1 gene provides type-defining sequence. Seven genotypes have been described which differ from each other by 1-2.5% of their DNA sequence overall (1). The regulatory region is "archetypal" in the urine, but extensively and uniquely rearranged in JCV strains obtained from productively infected brain tissue in the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML), now occurring mainly in AIDS patients.
Here we report studies of JCV from the highlands of Papua New Guinea (PNG) (20 samples) and from two ethnic groups on the neighboring island of New Britain: the non-Austronesian-speaking Baining people (14 samples) and the Austronesian-speaking Tolai people (21 samples). Twenty samples were also characterized from the Chamorro of Guam, a Micronesian population. Although JCV strains from PNG and Guam fell within the broad Asian group previously defined in the 5'-region of the VP1 gene as Type 2 and Type 7, all PNG strains were distinct from both genotypes (Figure). In contrast, among the 20 Chamorro JCV samples, 8 were like Type 7 strains found in south China and southeast Asia (Guam-1), while 9 strains were distinct from both mainland and most PNG strains (Guam-2). The difference between the PNG strains and those found among the Chamorro on Guam supports other evidence favoring more recent settlement of that part of Micronesia. We identified three JCV variants within Papua New Guinea (PNG-1, PNG-2 and PNG-3)(Table 1) which showed very different distributions. PNG-1 strains were present in all three populations (Highlanders, and the Baining and Tolai of New Britain), but PNG-2 strains were restricted to the Highlanders. The single PNG-3 strain, which was identified in a Tolai-speaking individual, is closely related to the Chamorro variant (Guam-2 strains). As the Tolai and the Chamorro both speak related Austronesian languages, it is possible that these strains originated in a common Austronesian ancestor. The restriction of PNG-2 variants to the highlands and their relative lack of DNA sequence variation in the regulatory region (Table 2) suggest that they arose comparatively recently there. These PNG-2 variants are characterized by a unique deletion with a nested duplication reminiscent of the changes previously seen mainly in the brains of progressive multifocal leukoencephalopathy (PML) patients. This is the first instance of a complex rearrangement (combined deletion and duplication) in JCV known to be excreted widely in a human population. A subtype within the PNG-2 group (PNG-2B) has a unique deletion in the agnoprotein gene that removes amino acids 57-63 of this 71 amino acid protein (2). We suggest that both the regulatory region rearrangement and the coding region (agnoprotein) deletion may have given these variants a selective advantage allowing relatively recent and rapid spread within the Highland population.
The AIDS epidemic is said to be gaining momentum in PNG. With it will come PML, the fatal neurological infection of glial cells, especially oligodendrocytes, by JCV. Careful surveillance of HIV-1 infected individuals for cause of death may reveal whether these unusual JCV variants in the PNG Highlands are, in addition to being more highly infectious, also more neurotropic.
References:
1. Agostini, H.T., Jobes, D.V., Chima, S.C., Ryschkewitsch, C.F., Stoner,
G.L. (1999) Natural and pathogenic variation in the JC virus genome. In: Recent
Research Developments in Virology, Transworld Research Network (in press).
2. Jobes, D.V., Friedlaender, J.S., Mgone, C.S., Koki, G., Alpers, M.P., Ryschkewitsch, C.F. Stoner, G.L. (1999) A novel JC virus variant found in the Highlands of Papua New Guinea has a 21-bp deletion in the agnoprotein gene. Journal of Human Virology (in press).
Abstract - Presented at the Virus Evolution Workshop
Ardmore, OK
October 21 - 24th, 1999
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e-mail: mroossinck@noble.org
Dr. Marilyn Roossinck
Plant Biology Division
The Noble Foundation
P.O. Box 2180
Ardmore, OK 73402
phone: 580 224-6630