F Wong-Staal

Human B-lymphotropic virus (human herpesvirus-6).

Human B-lymphotropic virus (HBLV), also known as human herpesvirus-6 (HHV-6) was first isolated in 1986 from AIDS patients and patients with other lymphoproliferative disorders. HBLV is distinct from known human herpesviruses, biologically, immunologically and by molecular analysis. HBLV can infect and replicate in fresh and established lines of hemopoietic cells and cells of neural origin, suggesting wide tropism. The prevalence of HBLV antibody in the normal population was 26% though clear differences between different populations were observed. The prevalence of HBLV antibody an elevated antibody titer was higher in sera from certain malignancies, Sjögrens syndrome and sarcoidosis. Antibody to HBLV was also elevated in AIDS patients and patients with chronic fatigue syndrome. HBLV-DNA was detected in some B-cell lymphomas. The broad in vitro tropism, combined with immunological and molecular evidence of HBLV infection in individuals raise the question of the pathogenicity of this virus in some diseases. Because in vitro co-infection of CD4 cells by HBLV and HIV leads to enhanced degeneration, this raises the possibility that infection in AIDS patients by both viruses can aggravate the HIV-induced immunodeficiency. Specific reagents and immunological and molecular assays are currently being investigated, which will aid in virus detection in cells from patients, and in elucidating the possible pathogenesis of HBLV.

T-Cell Lymphoproliferative Syndrome Associated with Human T-Cell Leukemia/Lymphoma Virus

Human T-cell leukemia/lymphoma virus is a unique family of T-cell tropic, human, type-C retroviruses. The discovery of this class of retroviruses provides the first proven link between retroviruses and cancer in humans. This virus is endemic in certain parts of the world, including the southeastern United States, and is associated with the development of adult T-cell leukemia/lymphoma, a fulminant lymphoproliferative disorder frequently accompanied by opportunistic infections and hypercalcemia. Over the last few years, major advances have been made in understanding the clinical, epidemiologic, molecular biologic, and immunologic features of this unique class of human RNA tumor viruses.

Polymerase chain reaction amplification and in situ hybridization for the detection of human B-lymphotropic virus

Polymerase chain reaction amplification (PCR) is a recently described technique that allows for the amplification of a given sequence of DNA. It can be used to reliably amplify sequences of up to 3 kb within hours. The amplified sequence can then be recognized by hybridization with a specific probe after transfer onto nitrocellulose or nylon paper. We used PCR to recognize human B-lymphotropic virus (HBLV or HHV-6) specific sequences in various tumors as well as in the blood of patients with AIDS. Sixty-three specimens of DNA extracted from peripheral blood of patients with AIDS as well as DNA extracted from various lymphoproliferative disorders were analysed; 52 out of 63 (83%) patients with AIDS were found to have amplification of the HHV-6 specific sequence; 2 out of the 63 (3%) had equivocal amplification and 9 (14%) were found to be negative. Twenty out of 23 tumors were found to have amplified HBLV-specific sequences. Only one of these tumors was positive by Southern hybridization on restriction enzyme digested genomic DNA. In situ hybridization of clinical specimens using radiolabelled RNA probes or hapten-labelled DNA probes was used to detect the presence of HBLV in tumors. Three tumors of B cell origin were found to be positive for HBLV.

Unintegrated and integrated proviruses of two strains of baboon endogenous viruses: Comparative restriction endonuclease analysis☆

Abstract We have deduced restriction enzyme maps of the unintegrated DNA of two strains of baboon endogenous virus, 455K and M7. These were isolated from two closely related species Papio anubis and Papio cynocephalus . Of the seven restriction enzymes used, Eco RI, Hin dIII, Pvu II, and Xho I gave conserved cleavage patterns for both genotypes. Xho I cuts within 400 nucleotides from both ends of the linear form. However, the cleavage sites for Bam HI, Sal I, and Bcl I are distinguishable for the two virus genomes. In addition to the linear 455K proviral DNA molecules which contain a direct terminal repeat of 0.6 ± 0.2 kolobases, two discrete species of circular proviral intermediates were also detected. One corresponds in size to the linear viral DN molecules and the other has a deletion of 600 base pairs mapping in the region of the 3′-5′ joint Xho I fragment. This deletion is probably equivalent to one unit of large terminal repeat sequences (LTR). We also examined the integrated proviruses in heterologous cells infected with M7 and 455K. The results indicate that the integrated proviruses are colinear with the virus genomes and retain both copies of LTR. The sites of integration are multiple in uncloned cells. Two cell clones examined carry three to five proviruses. These results are similar to previous studies of other integrated retroviruses. They also provide a comparative basis for examining the organization and divergence of the endogenous baboon virogenes in different primates. Those studies are presented in the accompanying paper.