Introduction and history of foot-and-mouth disease virus.

Foot-and-mouth disease (FMD) has been recognized as a significant epidemic disease threatening the cattle industry since the sixteenth century, and in the late nineteenth century it was shown by Loeffler and Frosch to be caused by a submicroscopic, filterable transmissible agent, smaller than any known bacteria. The agent causing FMD was thus the first virus of vertebrates to be discovered, soon after the discovery of tobacco mosaic virus of plants. It was not until 1920 that a convenient animal model for the study of FMD virus was established by Waldmann and Pape, using guinea-pigs, and with the later development of in vitro cell culture systems for the virus, the chemical and physical properties of FMD virus were elucidated during the remainder of the twentieth century, culminating in 1989 with a complete description of the three-dimensional structure of the virion. FMD virus is classified as a species in the Aphthovirus genus of the family Picornaviridae. The virus is acid labile, and the genome RNA contains a characteristic tract of polyC located about 360 nucleotides from the 5' terminus. Seven main serotypes exist throughout the world, as well as numerous subtypes. The World Reference Laboratory for FMD is located at Pirbright, Surrey, UK and undertakes surveillance of FMD epidemics by serotyping as well as by genotyping isolates of the virus. A major epidemic of FMD occurred in the UK in 2001 and was caused by a virulent strain of FMD virus with origins in Asia. The advantages and some disadvantages of controlling FMD outbreaks by vaccination are discussed.

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.

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)

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.

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.

Identification of the cap-binding protein of two strains of influenza A/FPV.

We have identified the cap-recognizing protein of two strains of influenza A fowl plague virus (FPV) by photoaffinity labelling of virion proteins with a photoreactive analogue of the 5'-methyl cap structure of messenger RNA. The cap-recognizing protein of influenza A/FPV/Rostock/34 is the P2 polypeptide, and that of influenza A/FPV/Dutch/27 (Dobson) is the P3 polypeptide. In each case the cap-recognizing protein is the product of RNA segment 1.

Nucleotide sequence of fowl plague virus RNA segment 7.

Nucleotide sequence analysis of a recombinant DNA clone of RNA segment 7 from FPV/Rostock/34 has shown it to be highly conserved in comparison with RNA segment 7 from two human strains (Allen et al., 1980; Winter & Fields, 1980; Lamb & Lai, 1981). FPV RNA segment 7 contains the coding capacity for two polypeptide chains. The sequence homology between RNA segment 7 of avian and human viruses was greater than 90%, and most of the changes did not result in amino acid substitutions.

Evidence for the involvement of influenza A (fowl plague Rostock) virus protein P2 in ApG and mRNA primed in vitro RNA synthesis.

Eleven temperature-sensitive (ts) mutants of influenza A (fowl plague, Rostock) virus were analysed for in vitro RNA transcriptase activity in reactions primed by ApG or globin mRNA at 31 degrees C or at 40.5 degrees C, the restrictive temperature for ts mutant growth. Only those ts mutants studied which were defective in RNA segment 1, coding for the virion P2 protein, were defective in RNA transcriptase activity when compared to wild-type virus. Mutants having a defect in the P2 protein had no significant RNA transcriptase activity in reactions at 40.5 degrees C primed by globin mRNA. However, one mutant showed RNA transcriptase activity similar to wild-type virus at 40.5 degrees C when ApG (0.3 mM) was used as primer. The results suggest that influenza (fowl plague, Rostock) P2 protein is directly involved in the mRNA priming reaction, as well as in the RNA transcription reaction in vitro.