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Biomedical subjects

B W Mahy

Publications and source records attributed to B W Mahy.

At least 19 recordsLinked to original sources
PubMed1996

The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing.

In late 1994 and early 1995, Ebola (EBO) virus dramatically reemerged in Africa, causing human disease in the Ivory Coast and Zaire. Analysis of the entire glycoprotein genes of these viruses and those of other EBO virus subtypes has shown that the virion glycoprotein (130 kDa) is encoded in two reading frames, which are linked by transcriptional editing. This editing results in the addition of an extra nontemplated adenosine within a run of seven adenosines near the middle of the coding region. The primary gene product is a smaller (50-70 kDa), nonstructural, secreted glycoprotein, which is produced in large amounts and has an unknown function. Phylogenetic analysis indicates that EBO virus subtypes are genetically diverse and that the recent Ivory Coast isolate represents a new (fourth) subtype of EBO virus. In contrast, the EBO virus isolate from the 1995 outbreak in Kikwit, Zaire, is virtually identical to the virus that caused a similar epidemic in Yambuku, Zaire, almost 20 years earlier. This genetic stability may indicate that EBO viruses have coevolved with their natural reservoirs and do not change appreciably in the wild.

Animals↗
PubMed1992

Recommendations of the International Roundtable Workshop on Bovine Spongiform Encephalopathy.

Recommendations of the working party were summarized as follows: Determine the status in all countries of their national cattle herds with respect to BSE. Attempt to develop a test to recognize BSE-infected animals before they become clinically ill. Establish procedures to prevent spread of BSE agent into the cattle populations, especially by eliminating feeds containing rendered ruminant proteins. Review the rendering processes, identify the sources and destinations of rendered products, and suggest appropriate changes if needed. Especially needed are standardized rendering procedures in regard to use of organic solvents, temperature, and duration of heat treatment. Review import and export regulations to reduce the risk of spreading BSE and to maximize opportunities for safe trading in cattle and cattle products. The scrapie-free certification program of the USDA was supported, and similar programs might be considered by other countries. If BSE/scrapie is diagnosed in a given country, determine baseline incidence of CJD in those countries and consider contributing to an international registry. The WHO should address the problems of BSE, formulate policy, participate in and coordinate research, and provide training opportunities for veterinary and human health care workers from eastern European countries and developing nations. Government and private agencies should consider increasing support for research on transmissibility and pathogenesis of CJD, BSE, CWD, scrapie, and transmissible mink encephalopathy. Prepare and publish a critical neuropathologic review of all spongiform encephalopathies, naturally and experimentally transmitted, defining the characteristics of each disease in the various species known to be susceptible. Consider producing guidelines for the biological and pharmaceutical industries with regard to sourcing, collecting, and processing bovine and ovine materials.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Virus zoonoses and their potential for contamination of cell cultures.

Silent virus infections of laboratory animals present a human health hazard, from direct exposure and from contamination of biological products for human use. Here we report two recent examples. In 1989, an outbreak of lymphocytic choriomeningitis virus (LCMV) infections was recognized among workers at a cancer research center after an animal caretaker developed viral meningitis. Investigation revealed that multiple tumor cell lines at the facility were infected with LCMV, as were research animals injected with these cell lines. Of 82 workers tested, eight (10%) were found to have been infected. The infected workers were more likely than other animal handlers to report handling athymic (nude) mice (p less than .0.007). The number of nude mice used in this facilty had increased five-fold in the previous year, possibly explaining the timing of the outbreak. This is the first reported LCMV outbreak since 1975, and the first to implicate nude mice as a source of human LCMV infections. In November 1989 and January 1990, infections caused by two distinct Ebola-like filoviruses were discovered in non-human primates at quarantine facilities in Virginia and Pennsylvania. Although 22 persons were considered to have high- or medium-risk exposures for Ebola infection, no Ebola-compatible illnesses occurred. One of the medium-risk persons had Ebola IgG antibodies confirmed by IFA and Western blot. Rigorous use of barrier precautions may have limited exposure and infection with these filoviruses. In February 1990, new groups of filovirus-infected monkeys were identified in Virginia and in Texas. Seroconversion occurred in four animal handlers, including one to very high titer, but again no illness was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Novel polypeptides encoded by influenza virus subgenomic (DI type) virion RNAs.

We have isolated a ts mutant of influenza A/FPV/Rostock/34 that induces the synthesis of a novel small polypeptide in infected cells. This polypeptide is encoded by a subgenomic virion RNA derived from RNA segment 3, apparently by internal deletion. A second polypeptide, similarly derived from RNA segment 1, was found only after in vitro translation of infected cell RNA. The subgenomic vRNAs we describe are probably similar to those found in influenza DI virus preparations. The possible role of 'subgenomic' polypeptides in DI virus-mediated interference is discussed.

Animals↗
PubMed1984

Capped mRNAs may stimulate the influenza virion polymerase by allosteric modulation.

Analogues of the mRNA 5'-terminal methyl cap structure were found to stimulate the influenza virion RNA-dependent RNA polymerase. The single nucleotide analogue m7GMP was incorporated into RNA during transcription in vitro, and the stimulatory effect was not additive with the primer ApG, suggesting that m7GMP stimulates the virion polymerase by priming virus-specific mRNA synthesis, as has been shown for ApG. By contrast, stimulation by m7G(5')ppp(5')m6AM2-O was additive with that by ApG, and we could not demonstrate incorporation of the similar analogue m7G(5')ppp(5')Am2-O into RNA during transcription. We propose that these dinucleotide cap analogues stimulate the virion polymerase by allosteric modulation, independent of priming. This stimulation can be abolished by mutation, without loss of other activities associated with the cap-dependent endonuclease.

Allosteric Regulation↗
PubMed1984

Molecular cloning of the nucleoprotein gene of canine distemper virus.

Messenger RNAs labelled in vivo in Vero cells infected with canine distemper virus were analysed by electrophoresis on 1.5% agarose gels containing 2 M-formaldehyde. Seven virus-specific RNA bands could be distinguished which were not sensitive to actinomycin D treatment and were confined to the polyadenylated RNA fraction. The most abundant virus-specific mRNA species had a molecular weight of 0.52 X 10(6) and its coding capacity was consistent with it being the mRNA for the most abundant virus-specific protein, the nucleoprotein. Polyadenylated RNA of this size class was purified by electrophoresis on a polyacrylamide gel and cloned into the PstI site of plasmid pBR322. A virus-specific clone obtained, clone 224, was then used to select messenger RNA from infected cells. The messenger RNA selected had a molecular weight of 0.52 X 10(6) and directed the synthesis of only the virus-specific nucleoprotein when used to stimulate a wheat germ cell-free system.

Animals↗
PubMed1983

Reverse transcriptase activity and particles of retroviral density in cultured canine lymphosarcoma supernatants.

Lymphoid tissue from 43 cases of canine lymphosarcoma and from 40 clinically normal dogs have been examined for markers of retrovirus infection. From 69-76% of culture supernatants from lymphosarcomas were shown to contain particles of retroviral density and to possess poly rC-oligo dG templated polymerase (reverse transcriptase) activity compared with 17-24% of culture supernatants from normal canine lymphoid cells. In 6 culture supernatants from cases of lymphosarcoma, high molecular weight 60-70S RNA was detected and shown to be found in association with this particulate reverse transcriptase activity. No such RNA was detected in 6 culture supernatants from normal canine lymphoid cells.

Animals↗
PubMed1983

RNA-dependent RNA polymerase activity in murine coronavirus-infected cells.

The multiplication of murine coronavirus strains A59 or JHM in Sac(-) cells was unaffected by the presence of alpha-amanitin at concentrations which inhibited the host cell DNA-dependent RNA polymerase activity. In cells infected with the A59 virus strain, actinomycin D-resistant RNA synthesis could readily be detected by pulse-labelling with [3H]uridine; this virus-specific RNA synthesis was not induced in the presence of the protein synthesis inhibitor anisomycin. A new RNA-dependent RNA polymerase activity was detected in the large particle fraction of A59 virus-infected cells. Optimal conditions for enzyme activity in vitro were established. Maximum activity occurred 5 h after infection, coincident with the peak of virus-specific RNA synthesis detected by pulse-labelling in vivo.

Amanitins↗
PubMed1982

Synthesis of RNA segments 1-3 during generation of incomplete influenza A (fowl plague) virus.

Incomplete influenza A virus (fowl plague Dobson strain) was prepared by undiluted passage in primary chick embryo fibroblast cells. Analysis of released virus RNA revealed a deficiency in RNA segments 1-3, characteristic of incomplete virus formation. The virus yield from a high multiplicity infection with standard virus always showed this deficiency, even when analysed as early as 6 hours post-infection, whereas infection at low multiplicity gave rise to virus indistinguishable in RNA composition from the parent virus. The relative amounts of intracellular, non-polyadenylated, complementary RNA (template RNA) were found to reflect accurately the eventual RNA composition of released virus, and were altered in phase with PFU:HAU ratio, throughout a von Magnus cycle.

Animals↗