PubMed Health⌕ Search

Biomedical subjects

R J Frisque

Publications and source records attributed to R J Frisque.

48 records · Page 3Linked to original sources
PubMed1985

Differences in regulatory sequences of naturally occurring JC virus variants.

The regulatory region was sequenced for DNAs representative of seven independent isolates of JC virus, the probable agent of progressive multifocal leukoencephalopathy. The isolates included an oncogenic variant (MAD-4), an antigenic variant (MAD-11), and two different isolates derived from the urine (MAD-7) and from the brain (MAD-8) of the same patient. The representative DNAs were molecularly cloned directly from diseased brain tissue and from human fetal glial cells infected with the corresponding isolated viruses. The regulatory sequences of these DNAs were compared with those of the prototype isolate, MAD-1, sequenced previously (R. J. Frisque, J. Virol. 46:170-176, 1983). We found that the regulatory region of JC viral DNA is highly variable due to complex alterations of the previously described 98-base-pair repeat of MAD-1 DNA. On the basis of these alterations, there are two general types of JC virus. There were no consistent alterations in regulatory sequences which could distinguish brain tissue DNAs from tissue culture DNAs. Furthermore, for each isolate except MAD-1 (R. J. Frisque, J. Virol. 46:170-176, 1983), the regulatory regions of brain tissue and tissue culture DNAs were not identical. The arrangement, sequence, or both of potential regulatory elements (TATA sequence, GGGXGGPuPu, tandem repeats) of JC viral DNAs are sufficiently different from those in other viral and eucaryotic systems that they may effect the unique properties of this slow virus.

Animals↗
PubMed1984

Human polyomavirus JC virus genome.

The complete DNA sequence of the human JC virus, which was found to consist of 5,130 nucleotide pairs, is presented. The amino acid sequence of six proteins could be deduced: the early, nonstructural proteins, large T and small t antigens; the late capsid proteins, VP1, VP2, and VP3; and the agnogene product encoded within the late leader sequence, called the agnoprotein in simian virus 40. The extent of homology between JC virus DNA and the genomes of simian virus 40 (69%) and BK virus (75%) confirmed the close evolutionary relationship of these three polyomaviruses. The sequences showing the greatest divergence in these viral DNAs occurred within the tandem repeats located to the late side of the replication origins.

Amino Acid Sequence↗
PubMed1983

Nucleotide sequence of the region encompassing the JC virus origin of DNA replication.

The region of the JC virus (JCV) genome from 0.58 to 0.73 map units was sequenced by the Maxam-Gilbert technique. This segment of DNA specifies several regulatory elements and the amino-terminal portion of the early viral proteins. Comparisons with the analogous regions in the polyomaviruses simian virus 40 (SV40) and BK virus (BKV) confirm the close evolutionary relationship of these three viruses. Similarities include palindromic and symmetrical sequences near their origins of DNA replication, binding sites for their large T proteins, an AT-rich region (the Goldberg-Hogness, or TATA, box), and a large tandem duplication or triplication to the late side of their replication origins (however, these sequences differ). Homology between the sequences coding for the early proteins is also evident (79 and 93 of the first 110 amino acids are shared with SV40 and BKV, respectively). Of greater interest are features of the JCV genome which differ from those of other polyomaviruses. Absent in JCV and BKV are sequences which resemble the third T-antigen binding site of SV40. In addition, a set of sequences present in JCV and BKV DNAs (33 nucleotides in JCV and 22 nucleotides in BKV) and located near a 17-base-pair palindrome shared by all three viruses is missing in SV40 DNA. Another sequence, GGGXGGAG, which is repeated several times in many polyomaviruses and adenoviruses and which is thought to play a role in DNA replication or transcription or both, is not found near the JCV origin of replication. Finally, the tandem repeat of JCV, unlike those of BKV and SV40, includes the Goldberg-Hogness sequence.

Amino Acid Sequence↗
PubMed1983

Regulatory sequences and virus-cell interactions of JC virus.

A set of recombinant DNAs, representing several isolates of JCV, has been constructed. Some of these cloned DNAs transform nonpermissive primary hamster brain cells. Analysis of the early viral mRNAs and proteins isolated from these transformants revealed similarities with the large and small T messages and proteins of SV40. The region of the JCV genome from 0.63 to 0.73 map units was sequenced by the Maxam-Gilbert technique. This segment of DNA specifies several regulatory elements and the amino-terminal portion of the early viral proteins. Comparisons with the analogous regions in the polyomaviruses SV40 and BKV, confirm the close evolutionary relationship of these three viruses. Similarities include palindromic and symmetrical sequences near the origins of DNA replication, binding sites for the large T proteins, and AT-rich region (the Goldberg-Hogness or TATA box), and a large tanden duplication or triplication to the late side of the replication origin (however, these sequences differ). Homology between the sequences coding for the early proteins is also evident (27 of the first 33 amino acids are shared). Of greater interest are features of the JCV genome which differ from those of other polyomaviruses. Absent in JCV and BKV are sequences which resemble the third T antigen-binding site of SV40. In addition, a set of sequences present in JCV and BKV DNA (33 nucleotides in JCV, 22 nucleotides in BKV), and located near a 17 base pair palindrome shared by all three viruses, is missing in SV40 DNA. Another sequence, GGGXGGAG, which is repeated several times in many polyomaviruses and adenoviruses, and which is thought to play a role in DNA replication and/or transcription, is not found in the JCV sequence presented. Finally, the tandem repeat of JCV, unlike those of BKV and SV40, includes the Goldberg-Hogness sequence.

Animals↗
PubMed1981

Identification of a promoter component involved in positioning the 5' termini of simian virus 40 early mRNAs.

The 5' termini of the principal early mRNAs produced in cells transformed by wild-type simian virus 40 lie 21-25 nucleotides downstream from an A-T-T-T-A-T sequence on the DNA template. The 5' termini of early mRNAs produced by five origin-defective mutants containing deletions downstream from the A-T-T-T-A-T sequence and one viable mutant dl892 with a deletion starting 15 nucleotides upstream from this sequence were determined by a method involving synthesis, separation, and determination of the sequences of DNAs complementary to 5' termini. Mutant dl892 produced early mRNAs with the same principal 5' termini as wild-type virus; the origin-defective mutants produced mRNAs with principal 5' termini shifted downstream by a distance equivalent to the length of the deleted DNA segment. These data suggest that a DNA sequence of 29 nucleotides, which includes the A-T-T-T-A-T sequence, contains a component(s) of a promoter for early transcription. This component functions in positioning the 5' ends of the principal early mRNAs 21-25 nucleotides downstream from the A-T-T-T-A-T sequence and acts independently of these downstream sequences.

Base Sequence↗
PubMed1980

Expression of early genes of origin-defective mutants of simian virus 40.

The nucleotide sequences of eight origin-defective mutants of simian virus 40 have been determined. All of the mutants have suffered deletions, which range in size from 4 to 241 nucleotides. Some of the mutants induce the synthesis of tumor (T) antigen, others do not. Viral mRNA extracted from rat cells transformed by two of the T-antigen-positive mutants has been analyzed by the S1 nuclease technique of Berk and Sharp. Irrespective of the size or the location of the deletions, the 5' ends of viral mRNAs are located approximately the same distance from the A+T-rich region (A-T-T-T-A-T) rather than at a specific site in the viral genome.

Antigens, Viral↗
PubMed1980

Origin-defective mutants of SV40.

We have described a new technique for the isolation and propagation of nonconditionally lethal mutants. We have used this method to generate mutants of SV40 that contain a defective origin of DNA replication. Using these mutants, we have established the following: (1) SV40 DNA replication and early transcription are functionally separate. (2) A functional viral origin of DNA replication is not necessary for the maintenance of transformation. (3) The lack of the origin of SV40 DNA replication does not affect the efficiency of transformation when nonpermissive cells are transfected by DNA using the calcium technique.

Animals↗
PubMed1979

Restriction endonuclease cleavage map of the DNA of JC virus.

A physical map of the sites cleaved by the following restriction endonucleases was derived for the DNA of JC virus, a human polyomavirus: EcoRI, HpaI, and PstI (one site each); HindII (four sites); and HindIII (three sites). By agarose gel electrophoresis of fragmented DNA, the size of full-length DNA of JC virus was estimated to be 5,125 +/- 105 base pairs (98 +/- 2% of the length of simian virus 40 DNA).

DNA Restriction Enzymes↗
PubMed1979

Infectivity of the DNA from four isolates of JC virus.

The infectivity of JC virus DNA was demonstrated in its most permissive cell culture, primary human fetal glial cells. The amount of infectivity observed in these heterogeneous cultures varied considerably between batches of cells. Contrary to results obtained with the papovaviruses simian virus 40 and BK virus, the calcium technique (F. L. Graham and A. J. van der Eb, Virology 52:456--467, 1973) was found to be more efficient at promoting JC virus DNA infectivity than the DEAE-dextran method (J. H. McCutchan and J. S. Pagano, J. Natl. Cancer Inst. 41:351--357, 1968): maximum infectivity titers of 4 x 10-(4) and 6 x 10(3) fluorescent cell units per microgram of DNA, respectively. These values represent an approximate recovery of infectivity from virus of between 0.02 and 0.14%. Comparisons of infectivity of DNAs obtained from four isolates of JC virus and which differed in their degrees of heterogeneity did not reveal significant differences. The JC virus DNA was not infectious in primary human fetal lung and kidney cells.

Antigens, Viral↗