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S F Josephs

Publications and source records attributed to S F Josephs.

69 records · Page 4Linked to original sources
PubMed1984

Human-proto-oncogene nucleotide sequences corresponding to the transforming region of simian sarcoma virus.

The nucleotide sequences of the six regions within the normal human cellular locus (c-sis) that correspond to the entire transforming region of the simian sarcoma virus (SSV) genome (v-sis) were determined. The regions are bounded by acceptor and donor splice sites and, except for region 6, resemble exons. Region 6 lacks a 3' donor splice site and terminates -5 base pairs from the 3' v-sis-helper-viral junction. This is consistent with a model proposing that SSV was generated by recombination between proviral DNA of a simian sarcoma associated virus and proto-sis and that introns were spliced out subsequently from a fused viral-sis messenger RNA. This also suggests that the 3' recombination occurred within an exon of the woolly monkey (Lagothrix) genome. The open reading frames predicting the v-sis and c-sis gene products coincide with the stop codon of c-sis located 123 nucleotides into the fifth region of homology. The overall nucleotide homology was 91 percent with substitutions mainly in the third codon positions within the open reading frame and with greatest divergence within the untranslated 3' portion of the sequences. The predicted protein products for v-sis and c-sis are 93 percent homologous. The predicted c-sis gene product is identical in 31 of 31 amino acids to one of the published sequences of platelet-derived growth factor. Thus, c-sis encodes one chain of human platelet-derived growth factor.

Amino Acid Sequence↗
PubMed1984

Nucleotide sequence of the large terminal repeat of two different strains of gibbon ape leukemia virus.

Gibbon ape leukemia virus, SEATO strain (GaLV-SEATO), a virus that induces myeloid leukemia in gibbon apes, and GaLV, San Francisco strain (GaLV-SF), a virus associated etiologically with lymphocytic leukemia in gibbon apes, have been molecularly cloned. The complete nucleotide sequence of the large terminal repeats (LTRs) of both viruses are reported and compared to the previously published nucleotide sequence of the LTR of another member of the same virus group, the simian sarcoma virus (SSV). Substantial homology is evident among all three LTR sequences. The most striking feature of the GaLV-SEATO LTR is the presence of a 45-bp tandem direct repeat in the U3 region, an area likely to contain transcriptional enhancers. Both GaLV-SEATO and GaLV-SF contain a deletion in U3 when compared to SSV. Each of the three LTRs differ from the other two by short deletions in R-U5 and short additions in U3, as well as by numerous point mutations. The possibility that the structural changes observed in the LTR contribute to the differences in the pathogenic effects of these viruses is discussed.

Animals↗
PubMed1984

Long terminal repeat structure of an American isolate of type I human T-cell leukemia virus.

Variation in the structure of the long terminal repeat (LTR) element of human T-cell leukemia virus (HTLV) types has been noted (M. Seiki, S. Hattori, Y. Hirayama, and M. Yoshida (1983), Proc. Natl. Acad. Sci. USA 80, 3618-3622; K. Shimotohno, D. W. Golde, M. Miwa, T. Sugimura, and I. S. Y. Chen (1984), Proc. Natl. Acad. Sci. USA 81, 1079-1083; J. Sodroski, M. Trus, D. Perkins, R. Patarca, F. Wong-Staal, E. Gelmann, R. Gallo, and W. Haseltine (1984), Proc. Natl. Acad. Sci. USA 81, 4617-4621). To determine whether HTLV isolates with similar disease associations, but from different geographic locations, exhibit a conserved LTR structure, the nucleotide sequence of the LTR of an American HTLV isolate from a patient with adult T-cell leukemia/lymphoma was obtained. Comparison of this LTR sequence to that of two Japanese HTLV isolates associated with a similar disease reveals a highly conserved organization of the U3, R, and U5 regions. The U. S. isolate differs from the Japanese viruses by only 15-16 bases out of 754 bases in the LTR region. These results show that Japanese HTLV isolates from patients with adult T-cell leukemia/lymphoma are members of the HTLV-I family and that LTRs of HTLV-I isolates are highly conserved. A 50-nucleotide imperfect direct repeat element is also identified in the U3 of the HTLV LTR distant from the cap site. The position and conserved nature of this sequence make it a likely candidate for a transcriptional enhancer.

Base Sequence↗
PubMedDate not supplied

Two strains of baboon endogenous virus demonstrate a high degree of genetic conservation.

Molecular clones of the baboon endogenous viruses 455K, from Papio anubis, and M7, from Papio cynocephalus, have been constructed from unintegrated viral DNA. Although two specific restriction sites do distinguish the two, detailed restriction maps are nearly identical and heteroduplex molecules show complete homology. The latter observations indicate that this endogenous retrovirus genome has been strongly conserved among different species of baboon.

Animals↗
PubMedDate not supplied

Transformation of NIH 3T3 cells by a human c-sis cDNA clone.

The mechanism of leukaemogenic transformation by human T-cell leukaemia/lymphoma virus (HTLV), a retrovirus implicated in the aetiology of certain adult T-cell leukaemias and lymphomas, is unknown but is conceivably associated with the expression of the cellular analogues of retroviral oncogenes. The HUT-102 cell line, derived from a cutaneous T-cell lymphoma and infected with HTLV, expresses several cellular oncogenes. It is unusual among haemopoietic cell lines in that one of these is c-sis, the gene from which the oncogene v-sis of the simian sarcoma virus was derived, and perhaps the gene for platelet-derived growth factor (PDGF). To explore the possible role of c-sis expression in HTLV-induced disease, we have obtained cDNA clones of c-sis from HUT-102 cells. Here we describe two such clones and report that one of them transforms NIH-3T3 cells. This is the first example of transformation of NIH-3T3 cells by a human onc gene other than c-ras or Blym, as well as the first demonstration of transformation by a human cDNA clone.

Animals↗
PubMedDate not supplied

Complete nucleotide sequence of the AIDS virus, HTLV-III.

The complete nucleotide sequence of two human T-cell leukaemia type III (HTLV-III) proviral DNAs each have four long open reading frames, the first two corresponding to the gag and pol genes. The fourth open reading frame encodes two functional polypeptides, a large precursor of the major envelope glycoprotein and a smaller protein derived from the 3'-terminus long open reading frame analogous to the long open reading frame (lor) product of HTLV-I and -II.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

The trans-activator gene of HTLV-III is essential for virus replication.

Studies of the genomic structure of human T-lymphotropic virus type III (HTLV-III) and related viruses, implicated as the causal agent of acquired immune deficiency syndrome (AIDS), have identified a sixth open reading frame in addition to the five previously known within the genome (gag, pol, sor, env and 3'orf). This gene, called tat-III, lies between the sor and env genes and is able to mediate activation, in a trans configuration, of the genes linked to HTLV-III long terminal repeat (LTR) sequences. We now present evidence that the product of tat-III is an absolute requirement for virus expression. We show that derivatives of a biologically competent molecular clone of HTLV-III, in which the tat-III gene is deleted or the normal splicing abrogated, failed to produce or expressed unusually low levels of virus, respectively, when transfected into T-cell cultures. The capacity of these tat-III-defective genomes was transiently restored by co-transfection of a plasmid clone containing a functional tat-III gene or by introducing the TAT-III protein itself. As HTLV-III and related viruses are the presumed causal agents of AIDS and associated conditions, the observation that tat-III is critical for HTLV-III replication has important clinical implications, and suggests that specific inhibition of the activity of tat-III could be a novel and effective therapeutic approach to the treatment of AIDS.

Deltaretrovirus↗
PubMedDate not supplied

Characterization of cellular proteins recognizing the HIV enhancer using a microscale DNA-affinity precipitation assay.

Numerous nucleic acid sequence motifs have been identified as transcriptional regulatory elements, and proteins involved in the control of gene replication and transcription have been successfully purified using nucleic acid affinity procedures. We have developed an assay that allows direct characterization of cellular proteins binding to the enhancer element of the human immunodeficiency virus (HIV), which is analogous to immunoprecipitation techniques. In extracts of H9 cells, a human CD4+ lymphoblast line clonally selected for its ability to support HIV replication, we find a class of proteins that interact specifically with the HIV enhancer. Reproducible high-resolution, two-dimensional gel electrophoresis has allowed us to resolve these proteins into two major sets. One set is common to H9 cells, two human B-lymphoblast lines, and a phytohaemagglutinin (PHA)-stimulated human CD4+ lymphoblast line (Jurkat). A second set of proteins is found only in H9 cells. Thus, with this assay we have identified HIV enhancer-binding proteins that are constitutive or inducible and that are cell-type specific.

Base Sequence↗
PubMedDate not supplied

Human herpesvirus-6 (HHV-6) (short review).

Human Herpesvirus-6 is the etiological agent of Roseola infantum and approximately 12% of heterophile antibody negative infectious mononucleosis. HHV-6 is T-lymphotropic, and readily infects and lyses CD4+ cells. The prevalence rate of HHV-6 in the general population is about 80% (as measured by IFA) with an IgG antibody titer of 1:80. A lower prevalence, however, is observed in some countries. HHV-6 is reactivated in various malignant and non-malignant diseases as well as in Chronic Fatigue Syndrome and transplant patients. Furthermore, elevated antibody titers were also observed in lymphoproliferative disorders, auto-immune diseases and HIV-1 positive AIDS patients. There appears to be some strain variability in HHV-6 isolates. The GS isolates of HHV-6 (prototype) was resistant to Acyclovir, Gancyclovir, but its replication was inhibited by Phosphonoacetic acid and Phosphoformic acid. HHV-7 isolated from healthy individuals showed, by restriction analysis, that 6 out of 11 probes derived from two strains of HHV-6, cross-hybridized with DNA fragments, derived from HHV-7.

Genes, Viral↗
PubMedDate not supplied

Clinical indications and diagnostic techniques of human herpesvirus-6 (HHV-6) infection.

The sixth member of the human herpesvirus family, HHV-6, causes early childhood infection with subsequent latency and antibody prevalence of about 60-80%. Active infection is related to a number of acute and chronic diseases such as exanthem subitum, certain cases of infectious mononucleosis and other immunoproliferative syndromes, autoimmune disorders and so-called postinfectious chronic fatigue syndrome. The clinical diagnosis of HHV-6 associated diseases requires detailed clinical differential diagnostic procedures and meticulous serological testing with exclusion of other herpesvirus infections or cross-reactivity between such infections. Diagnostic efforts, however, are warranted by certain indications for therapeutic intervention. The current review summarizes indications, techniques and limitations for the serological diagnosis of HHV-6 infection.

Age Factors↗