4,552 publications from this institution
Abstract The effect of interferon on the synthesis and release of A‐, B‐ and C‐type viruses by oncornavirus carrier lines was studied. Murine cell lines were selected which carry either of these viruses and are sensitive to the antiviral effect of interferon, as measured by inhibition of vesicular stomatitis virus. Release of C‐type virus was found to be highly sensitive. Release of B‐type virus, on the contrary, was only marginally inhibited. Synthesis of intracisternal A‐type particles was finally not inhibited by interferon pretreatment. These differences between infectious C‐type and non‐infectious A‐ and B‐type viruses may reflect fundamental differences in the synthesis of these viruses.
The effect of E-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU) on herpes simplex virus (HSV) replication was examined and compared with that of E-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd). The 50% inhibitory dose against HSV type 1 (HSV-1) was 0.1 microgram/ml compared with 0.008 microgram/ml for BVdUrd; the antimetabolic 50% inhibitory dose of BVaraU ranged from 20 to 95 micrograms/ml. The addition of 50 micrograms of BVaraU per ml to HSV-1-infected Vero cells decreased the synthesis of viral and cellular DNA by 37 and 28%, respectively. The 5'-triphosphate (BVaraUTP) competed with dTTP in DNA synthesis by the herpes-viral and cellular DNA polymerases; the apparent Ki values of HSV-1 DNA polymerase, DNA polymerase alpha, and DNA polymerase beta were 0.14, 0.32, and 5 microM, respectively. Thus, BVaraU was a less effective antiherpesvirus agent than BVdUrd; unlike BVdUrd, it did not appear to be internally incorporated into replicating DNA in virus-infected cells.
A Raman-Ramsey Cs cell atomic clock is presented. The relaxation times of the population and the hyperfine coherences in the cell are measured. The effect on the central Ramsey fringe amplitude of the critical experimental parameters such as laser intensity, magnetic field, temperature, and Ramsey time is investigated. The existence and impact of the additional Deltam = 2 transitions involved in the pumping scheme are pointed out. Narrow resonance linewidths as low as 33 Hz with reasonable signal-to-noise ratios have been recorded. By removing a frequency drift attributed to the cell, the achieved frequency stability is 7 times 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-13</sup> tau <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1/2</sup> . The main noise contributions that limit the short-term frequency stability are reviewed and estimated.
Of a series of 58 aliphatic nucleoside analogues, (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA] proved to be the most active congener, when assayed for antiviral activity in primary rabbit kidney cell cultures challenged with either vaccinia or vesicular stomatitis virus. Whereas most analogues derived from substituted purine and pyrimidine bases and bearing various hydroxy- or amino-substituted alkyl chains did not show evidence of antiviral activity at a concentration of 2 mM, (S)-DHPA inhibited both vaccinia and vesicular stomatitis virus replication at 0.05-0.1 mM. For 9-[(RS)-2,3-diazidopropyl]adenine and some di- and trihydroxybutyl analogues of DHPA, viz., 9-[(2RS,3SR)-2,3-dihydroxybutylladenine, 9-[(RS)- or 9-[(S)-3,4-dihydroxybutyl]adenine, 9-[(2S,3R)-2,3,4-trihydroxybutyl]adenine, and 3-(adenin-9-yl)-(RS)-alanine, an antiviral effect was noted at a concentration of 0.5-1 mM.
Poly (2-azaadenylic acid) [(aza2A)n] and poly(2-azainosinic acid [(aza2I)n], two newly synthesized analogues of (A)n and (I)n, in which CH-2 of the purine ring is replaced by a nitrogen atom, have been evaluated in various biological assay systems. (Aza2A) n formed a complex with (U)n and (br5U)n, and (aza2I)n formed a complex with (C)n and (br5C)n, but these complexes were markedly destabilized relative to the corresponding (A)n or (I)n complexes. The (aza2A)n-and (aza2I)n-derived complexes failed to stimulate the production of interferon in primary rabbit kidney cells and human diploid fibroblasts, under conditions (A)n. (U)n, (I)n. (C)n and (I)n. (br5C)n induced high amounts of interferon. both (aza2A)n and (aza2I)n exerted a marked inhibitory effect on the endogenous RNA directed DNA polymerase (reverse transcriptase) activity associated with murine leukemia virus. They caused a relatively mild inhibition of complement activity in an hemolytic assay system.
The phosphonylmethoxyalkyl derivatives (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)adenine (PMEA), and 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) were evaluated for their in vivo efficacies in several animal model infections, i.e., mice infected intravenously with vaccinia virus and mice infected intracutaneously, intraperitoneally, or intracerebrally with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) or thymidine kinase-deficient (TK-) HSV-1. (S)-HPMPA inhibited the development of tail lesions caused by vaccinia virus if it was administered intraperitoneally or subcutaneously at a dosage as low as 5 mg/kg per day. All three compounds completely suppressed the development of skin lesions and the mortality associated therewith in hairless or athymic nude mice inoculated intracutaneously with HSV-1 or TK- HSV-1, if they were administered topically at a concentration as low as 0.1%; when (S)-HPMPA was applied topically at a concentration of greater than or equal to 0.3%, it completely abrogated mortality resulting from intracutaneous HSV-2 infection. Most dramatic were the effects shown by the compounds in mice inoculated intracerebrally with HSV-1, HSV-2, or TK- HSV-1, in which all three compounds given intraperitoneally at a dose of 50 or 100 mg/kg per day effected a significant reduction in the mortality rate of HSV-1-infected mice. The mortality of mice infected intracerebrally with HSV-2 or TK- HSV-1 was significantly reduced even when (S)-HPMPA was given at doses as low as 10 mg/kg per day. These data point to the great potential of the phosphonylmethoxyalkylpurines for both topical and parenteral treatment of HSV-1, HSV-2, and TK- HSV-1 infections.
