Strain variability among Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genomes: evidence that a large cohort of United States AIDS patients may have been infected by a single common isolate.
Previous analysis of the majority of Kaposi's sarcoma (KS) tumors, in both AIDS and non-AIDS populations, has revealed the consistent presence of two small subsegments (open reading frame 25/26 [ORF25/26] and ORF75) of a novel human gamma class herpesvirus genome referred to as KSHV or HHV-8. We have carried out DNA sequence comparisons with DNAs encompassing a total of 2,500 bp each over three separate PCR-amplified fragments from KS lesions and body cavity-based lymphoma (BCBL) samples from 12 distinct patients, including four African and two classical or endemic non-AIDS KS samples. The results revealed differences at 37 of 2,500 nucleotide positions (i.e., 1.5% overall variation). However, the 12 HHV-8 genomes examined fell into three distinct but very narrow subgroupings (A, B, and C strains). All A strain isolates differed from B strain isolates at 16 positions, but of the eight U.S. samples tested, six were A strains, and these differed at no more than two positions among them. Similarly, three of the four African samples were B strains, which differed from each other at only one position. The two C strain genomes also displayed only one nucleotide variation, but they differed from all A strains at 26 positions and from all B strains at 20 positions. One C strain genome was present in all six independent lesions from an AIDS KS patient with disseminated disease, and the other represented a mosaic A/C recombinant genome from the HBL6 cell line derived from a BCBL tumor. Evaluation of previous data suggests that B and C strains may predominate in Africa and that A strains predominate in classical Mediterranean samples. Although both B and C strains are represented in U.S. AIDS patients, the majority (70 to 80%) of samples from the mid-East Coast region at least appear to be virtually identical, supporting the concept that they may all derive from the spread during the AIDS epidemic of a single recently transmitted infectious agent.
Zong
J C
JC
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Metroka
C
C
Reitz
M S
MS
Nicholas
J
J
Hayward
G S
GS
D017088:AIDS-Related Opportunistic Infections / Q000821:virology*; D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology; D001483:Base Sequence; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D018142:Gammaherpesvirinae / Q000235:genetics; D014644:Genetic Variation; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011995:Recombination, Genetic; D012514:Sarcoma, Kaposi / Q000821:virology*; D014481:United States / Q000453:epidemiology
D004279:DNA, Viral